MENU
The Electronic Scholarly Publishing Project: Providing world-wide, free access to classic scientific papers and other scholarly materials, since 1993.
More About: ESP | OUR CONTENT | THIS WEBSITE | WHAT'S NEW | WHAT'S HOT
ESP: PubMed Auto Bibliography 17 Jun 2026 at 01:48 Created:
Evolution of Multicelluarity
Created with PubMed® Query: ( (evolution OR origin) AND (multicellularity OR multicellular) NOT 33634751[PMID] ) NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2026-06-15
Herbal medicine for melanin regulation: biological synthesis, effective formulas/compounds, and biopharmaceutical methods.
Journal of natural medicines, 80(1):1-25.
Melanin is omnipresent across diverse taxa in the biosphere, spanning microorganisms to multicellular eukaryotes. This pervasive distribution reflects its multifaceted roles, encompassing pigmentation, radical quenching, photoprotective barriers and immunomodulatory activity. The process of melanin biosynthesis can be simply defined as the conversion of tyrosine into melanin through a complex series of steps in melanosomes within melanocytes. Skin pigmentation results from melanin production by melanocytes in the epidermis. With the development of society, people are becoming increasingly concerned about their skin appearance, particularly issues related to pigmentation and skin radiance. Elevated melanin levels may lead to skin disorders associated with excessive pigmentation, including age spots, freckles and even melanoma, which cause distress and lower the life quality. In recent years, the high demand for skin whitening and brightening has promoted the exploration of whitening active ingredients and melanin biosynthesis mechanisms. In this paper, the biosynthetic signaling pathways, generating factors, active natural compounds and advanced delivery system related to the deposition of melanin were systematically reviewed. Moreover, we were the first to introduce Chinese herbal formulas, TCM therapeutic techniques, and several advanced delivery systems designed to enhance the transdermal absorption of traditional Chinese medicines. The ideology, technologies and herbal drugs originated from Chinese medicine are expected to be an important development field for skin whitening and pigmentation prevention.
Additional Links: PMID-41353249
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid41353249,
year = {2026},
author = {Wang, H and Jiang, J and Kang, W and Zhao, B and Ma, Y},
title = {Herbal medicine for melanin regulation: biological synthesis, effective formulas/compounds, and biopharmaceutical methods.},
journal = {Journal of natural medicines},
volume = {80},
number = {1},
pages = {1-25},
pmid = {41353249},
issn = {1861-0293},
support = {81703773//National Natural Science Foundation of China/ ; BK20170560//Natural Science Foundation of Jiangsu Province/ ; },
abstract = {Melanin is omnipresent across diverse taxa in the biosphere, spanning microorganisms to multicellular eukaryotes. This pervasive distribution reflects its multifaceted roles, encompassing pigmentation, radical quenching, photoprotective barriers and immunomodulatory activity. The process of melanin biosynthesis can be simply defined as the conversion of tyrosine into melanin through a complex series of steps in melanosomes within melanocytes. Skin pigmentation results from melanin production by melanocytes in the epidermis. With the development of society, people are becoming increasingly concerned about their skin appearance, particularly issues related to pigmentation and skin radiance. Elevated melanin levels may lead to skin disorders associated with excessive pigmentation, including age spots, freckles and even melanoma, which cause distress and lower the life quality. In recent years, the high demand for skin whitening and brightening has promoted the exploration of whitening active ingredients and melanin biosynthesis mechanisms. In this paper, the biosynthetic signaling pathways, generating factors, active natural compounds and advanced delivery system related to the deposition of melanin were systematically reviewed. Moreover, we were the first to introduce Chinese herbal formulas, TCM therapeutic techniques, and several advanced delivery systems designed to enhance the transdermal absorption of traditional Chinese medicines. The ideology, technologies and herbal drugs originated from Chinese medicine are expected to be an important development field for skin whitening and pigmentation prevention.},
}
RevDate: 2026-06-15
Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.
Journal of molecular evolution, 94(2):286-303.
This review explores codon usage bias, the non-random preference for synonymous codons, as a fundamental aspect of gene regulation, translation efficiency, and genome evolution in eukaryotes. Unlike prokaryotes, eukaryotic codon usage is influenced by GC content, gene expression levels, tRNA availability, and selection pressures. Evolutionarily, mutation, genetic drift, and natural selection shape codon preferences, leading to distinct biases across unicellular and multicellular organisms. Fungi, plants, and animals exhibit lineage-specific codon usage, often linked to translational efficiency and environmental adaptation via optimized protein production. Additionally, organelle genomes such as mitochondria and chloroplasts retain unique codon patterns due to their endosymbiotic origins. Beyond evolutionary roles, codon bias impacts human health, contributing to genetic diseases, cancer progression, and neurodegenerative disorders, distinct from its applications in gene therapy and vaccine design. Advances in computational approaches, including indices like Effective number of codons (ENC), Codon adaptation index (CAI), and Relative synonymous codon usage (RSCU), along with machine learning models and specialized databases, have enhanced codon usage analysis, providing insights into gene expression and functional genomics. Despite significant progress, many aspects of eukaryotic codon usage remain unexplored, presenting new opportunities in biotechnology, synthetic biology, and genomic research. A deeper understanding of codon bias can improve translational control strategies and optimize gene expression for therapeutic and industrial applications.
Additional Links: PMID-41779208
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid41779208,
year = {2026},
author = {Dahal, U and Shakya, R and Kour, B and Khanal, B and Singh, B},
title = {Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.},
journal = {Journal of molecular evolution},
volume = {94},
number = {2},
pages = {286-303},
pmid = {41779208},
issn = {1432-1432},
abstract = {This review explores codon usage bias, the non-random preference for synonymous codons, as a fundamental aspect of gene regulation, translation efficiency, and genome evolution in eukaryotes. Unlike prokaryotes, eukaryotic codon usage is influenced by GC content, gene expression levels, tRNA availability, and selection pressures. Evolutionarily, mutation, genetic drift, and natural selection shape codon preferences, leading to distinct biases across unicellular and multicellular organisms. Fungi, plants, and animals exhibit lineage-specific codon usage, often linked to translational efficiency and environmental adaptation via optimized protein production. Additionally, organelle genomes such as mitochondria and chloroplasts retain unique codon patterns due to their endosymbiotic origins. Beyond evolutionary roles, codon bias impacts human health, contributing to genetic diseases, cancer progression, and neurodegenerative disorders, distinct from its applications in gene therapy and vaccine design. Advances in computational approaches, including indices like Effective number of codons (ENC), Codon adaptation index (CAI), and Relative synonymous codon usage (RSCU), along with machine learning models and specialized databases, have enhanced codon usage analysis, providing insights into gene expression and functional genomics. Despite significant progress, many aspects of eukaryotic codon usage remain unexplored, presenting new opportunities in biotechnology, synthetic biology, and genomic research. A deeper understanding of codon bias can improve translational control strategies and optimize gene expression for therapeutic and industrial applications.},
}
RevDate: 2026-06-15
CmpDate: 2026-06-15
Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings.
PLoS computational biology, 22(6):e1014370 pii:PCOMPBIOL-D-25-01344.
Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters - cell division, differentiation, and death rates - from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.
Additional Links: PMID-42258486
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42258486,
year = {2026},
author = {Pilarski, J and Stadler, T and Seidel, S},
title = {Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings.},
journal = {PLoS computational biology},
volume = {22},
number = {6},
pages = {e1014370},
doi = {10.1371/journal.pcbi.1014370},
pmid = {42258486},
issn = {1553-7358},
mesh = {*Phylogeny ; *Cell Lineage/genetics ; Bayes Theorem ; *Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Computer Simulation ; *Single-Cell Analysis/methods ; Computational Biology ; Cell Division/genetics ; Population Dynamics ; Cell Differentiation/genetics ; *CRISPR-Cas Systems/genetics ; },
abstract = {Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters - cell division, differentiation, and death rates - from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Phylogeny
*Cell Lineage/genetics
Bayes Theorem
*Clustered Regularly Interspaced Short Palindromic Repeats/genetics
Computer Simulation
*Single-Cell Analysis/methods
Computational Biology
Cell Division/genetics
Population Dynamics
Cell Differentiation/genetics
*CRISPR-Cas Systems/genetics
RevDate: 2026-06-13
CmpDate: 2026-06-13
Identification of WRKY transcription factors (TFs) in the recretohalophyte Tamarix chinensis and functional analysis of TcWRKY13 under salt stress.
Plant cell reports, 45(7):.
We identified 37 TcWRKY genes and analyzed their bioinformatics features. TcWRKY13 enhances salt tolerance by affecting ion accumulation, strengthening antioxidant defenses, and reducing ROS accumulation. Tamarix chinensis, a typical woody recretohalophyte, exhibits high salt tolerance by secreting salt through its multicellular salt glands. WRKY transcription factors (TFs) play critical roles in plant stress responses; however, their functions in T. chinensis remain unclear. In this study, 37 TcWRKY genes were identified from transcriptome datasets of T. chinensis. The results showed that all TcWRKY proteins are hydrophilic and liposoluble proteins, with lengths ranging from 97 to 761 amino acids (aa). Based on conserved domain characteristics, these members were classified into three groups, all of which contain the WRKYGQK core sequence and zinc finger structures. The results of the RNA-seq and quantitative real-time polymerase chain reaction experiments exhibited that TcWRKY13 was one of the genes most significantly responsive to salt stress. Subcellular localization experiments suggested that TcWRKY13 may be localized to both the nucleus and the cell membrane in tobacco leaves. Functional analyses demonstrated that transient overexpression of TcWRKY13 significantly enhanced salt tolerance in T. chinensis, whereas virus-induced gene silencing (VIGS) of TcWRKY13 reduced salt tolerance. Furthermore, heterologous overexpression of TcWRKY13 from T. chinensis in Arabidopsis thaliana enhanced salt tolerance, as evidenced by a reduced rise in Na[+]/K[+] ion accumulation, elevated antioxidant enzyme activity, and reduced reactive oxygen species (ROS) accumulation. This study provides identification of the expressed WRKY genes under salt stress in T. chinensis and reveals the positive salt-tolerant function of TcWRKY13, offering a theoretical foundation for molecular breeding of crop glycophytes.
Additional Links: PMID-42270849
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42270849,
year = {2026},
author = {Xu, X and Yin, N and Jiang, C and Guan, L and Chen, Y and Han, S and Jin, Q and Shen, Y and Du, Q and Zhang, G},
title = {Identification of WRKY transcription factors (TFs) in the recretohalophyte Tamarix chinensis and functional analysis of TcWRKY13 under salt stress.},
journal = {Plant cell reports},
volume = {45},
number = {7},
pages = {},
pmid = {42270849},
issn = {1432-203X},
mesh = {*Tamaricaceae/genetics/physiology/metabolism ; *Transcription Factors/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant/drug effects ; Salt Tolerance/genetics ; *Salt Stress/genetics ; Plants, Genetically Modified ; Phylogeny ; Reactive Oxygen Species/metabolism ; Amino Acid Sequence ; Nicotiana/genetics ; Gene Expression Profiling ; },
abstract = {We identified 37 TcWRKY genes and analyzed their bioinformatics features. TcWRKY13 enhances salt tolerance by affecting ion accumulation, strengthening antioxidant defenses, and reducing ROS accumulation. Tamarix chinensis, a typical woody recretohalophyte, exhibits high salt tolerance by secreting salt through its multicellular salt glands. WRKY transcription factors (TFs) play critical roles in plant stress responses; however, their functions in T. chinensis remain unclear. In this study, 37 TcWRKY genes were identified from transcriptome datasets of T. chinensis. The results showed that all TcWRKY proteins are hydrophilic and liposoluble proteins, with lengths ranging from 97 to 761 amino acids (aa). Based on conserved domain characteristics, these members were classified into three groups, all of which contain the WRKYGQK core sequence and zinc finger structures. The results of the RNA-seq and quantitative real-time polymerase chain reaction experiments exhibited that TcWRKY13 was one of the genes most significantly responsive to salt stress. Subcellular localization experiments suggested that TcWRKY13 may be localized to both the nucleus and the cell membrane in tobacco leaves. Functional analyses demonstrated that transient overexpression of TcWRKY13 significantly enhanced salt tolerance in T. chinensis, whereas virus-induced gene silencing (VIGS) of TcWRKY13 reduced salt tolerance. Furthermore, heterologous overexpression of TcWRKY13 from T. chinensis in Arabidopsis thaliana enhanced salt tolerance, as evidenced by a reduced rise in Na[+]/K[+] ion accumulation, elevated antioxidant enzyme activity, and reduced reactive oxygen species (ROS) accumulation. This study provides identification of the expressed WRKY genes under salt stress in T. chinensis and reveals the positive salt-tolerant function of TcWRKY13, offering a theoretical foundation for molecular breeding of crop glycophytes.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Tamaricaceae/genetics/physiology/metabolism
*Transcription Factors/genetics/metabolism
*Plant Proteins/genetics/metabolism
Gene Expression Regulation, Plant/drug effects
Salt Tolerance/genetics
*Salt Stress/genetics
Plants, Genetically Modified
Phylogeny
Reactive Oxygen Species/metabolism
Amino Acid Sequence
Nicotiana/genetics
Gene Expression Profiling
RevDate: 2026-06-12
Inter-Organ Communication Networks in Systemic Physiology: Glucocorticoid Receptor α as a Central Integrator of Homeostasis.
International journal of molecular sciences, 27(11): pii:ijms27114702.
The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome-gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome-host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction-Priming, Modulatory, and Restorative-within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness.
Additional Links: PMID-42278234
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42278234,
year = {2026},
author = {Meduri, GU},
title = {Inter-Organ Communication Networks in Systemic Physiology: Glucocorticoid Receptor α as a Central Integrator of Homeostasis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {11},
pages = {},
doi = {10.3390/ijms27114702},
pmid = {42278234},
issn = {1422-0067},
abstract = {The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome-gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome-host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction-Priming, Modulatory, and Restorative-within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness.},
}
RevDate: 2026-06-12
Ancient conservation of androglobin expression reveals its evolutionary link to ciliary processes.
Molecular biology and evolution pii:8707197 [Epub ahead of print].
Androglobin (Adgb) is the most distinctive member of the globin superfamily. Its characteristic globin domain is permuted, interrupted by a calmodulin-binding motif, and embedded within a large multi-domain protein of ∼1500 amino acids that also contains a calpain protease domain. Initially described as testis-specific in mammals, Adgb is also expressed in ciliated epithelia of the female reproductive tract, lung, and brain, and knockout studies reveal its pivotal role during spermatogenesis. To trace its evolutionary origin, we performed comprehensive phylogenetic analysis across diverse eukaryotic taxa. Adgb is present in all major flagellated eukaryotic lineages but absent from non-flagellated clades. Orthology analysis indicates Adgb has been maintained as a predominantly single-copy gene across >1 billion years of evolution - a pattern contrasting sharply with other globins that underwent repeated duplication and functional diversification. Analysis of publicly available transcriptomes from early-branching metazoans confirmed robust Adgb expression in ciliated cell types and provides evidence for its regulation by the ancient ciliogenic transcription factor cRFXa in the choanoflagellate Salpingoeca rosetta. RNA in situ hybridization validated these findings, and comparative analyses suggest that ancestral Adgb homologues lacked the permuted globin domain found in metazoans. Collectively, our results demonstrate that Adgb exemplifies a rare evolutionary trajectory where structural innovation (domain permutation and fusion) enabled functional specialization while being an integral part of the non-redundant ciliary machinery. Adgb thus illustrates how constraint and innovation combine to shape the long-term fate of a protein.
Additional Links: PMID-42284459
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42284459,
year = {2026},
author = {Osterhof, C and Teschner, D and Balling, M and Herwig, A and Duda, C and Botton-Amiot, G and Hildebrandt, A and Sprecher, S and Hankeln, T and Hoogewijs, D},
title = {Ancient conservation of androglobin expression reveals its evolutionary link to ciliary processes.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msag147},
pmid = {42284459},
issn = {1537-1719},
abstract = {Androglobin (Adgb) is the most distinctive member of the globin superfamily. Its characteristic globin domain is permuted, interrupted by a calmodulin-binding motif, and embedded within a large multi-domain protein of ∼1500 amino acids that also contains a calpain protease domain. Initially described as testis-specific in mammals, Adgb is also expressed in ciliated epithelia of the female reproductive tract, lung, and brain, and knockout studies reveal its pivotal role during spermatogenesis. To trace its evolutionary origin, we performed comprehensive phylogenetic analysis across diverse eukaryotic taxa. Adgb is present in all major flagellated eukaryotic lineages but absent from non-flagellated clades. Orthology analysis indicates Adgb has been maintained as a predominantly single-copy gene across >1 billion years of evolution - a pattern contrasting sharply with other globins that underwent repeated duplication and functional diversification. Analysis of publicly available transcriptomes from early-branching metazoans confirmed robust Adgb expression in ciliated cell types and provides evidence for its regulation by the ancient ciliogenic transcription factor cRFXa in the choanoflagellate Salpingoeca rosetta. RNA in situ hybridization validated these findings, and comparative analyses suggest that ancestral Adgb homologues lacked the permuted globin domain found in metazoans. Collectively, our results demonstrate that Adgb exemplifies a rare evolutionary trajectory where structural innovation (domain permutation and fusion) enabled functional specialization while being an integral part of the non-redundant ciliary machinery. Adgb thus illustrates how constraint and innovation combine to shape the long-term fate of a protein.},
}
RevDate: 2026-06-12
Evolutionary transition from single-cell to multi-cell organisms: the role of surface waters and their hydrodynamics.
Scientific reports pii:10.1038/s41598-026-57306-7 [Epub ahead of print].
The evolutionary transition from unicellular to multicellular organisms exhibited a sharp increase in metabolic rates, yet the physical conditions supporting this transition remain poorly understood. Here we propose that wide-spread hydrodynamic enhancement of nutrient delivery to the microorganisms in the Neoproterozoic Era constituted a necessary enabling condition for early multicellularity, complementing the effect of rising oxygen levels occurring at the same time. Along with conceptual arguments in support of this hypothesis, we define three testable hydrodynamic mechanisms (viscous-diffusive, viscous-convective, and inertial-convective) controlling nutrient uptake and largely applicable for both bed-attached and free-floating microorganisms. We also highlight a flow-bed interface in surface streams as potentially important hotbed for multicellularity breeding, complementing the mainstream perception on the defining role of early oceans. Overall, our results emphasize hydrodynamics as under-represented physical component in existing evolutionary frameworks and generate testable predictions linking organism size, flow conditions, and habitat type.
Additional Links: PMID-42286166
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42286166,
year = {2026},
author = {Nikora, V and Fang, H and He, G and Huang, L},
title = {Evolutionary transition from single-cell to multi-cell organisms: the role of surface waters and their hydrodynamics.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-57306-7},
pmid = {42286166},
issn = {2045-2322},
support = {EP/V002414/1//Engineering and Physical Sciences Research Council (EPSRC), UK/ ; 2022YFC3201803//National Key Research and Development Program of China/ ; 12272209 and U2040214//National Natural Science Foundation of China/ ; },
abstract = {The evolutionary transition from unicellular to multicellular organisms exhibited a sharp increase in metabolic rates, yet the physical conditions supporting this transition remain poorly understood. Here we propose that wide-spread hydrodynamic enhancement of nutrient delivery to the microorganisms in the Neoproterozoic Era constituted a necessary enabling condition for early multicellularity, complementing the effect of rising oxygen levels occurring at the same time. Along with conceptual arguments in support of this hypothesis, we define three testable hydrodynamic mechanisms (viscous-diffusive, viscous-convective, and inertial-convective) controlling nutrient uptake and largely applicable for both bed-attached and free-floating microorganisms. We also highlight a flow-bed interface in surface streams as potentially important hotbed for multicellularity breeding, complementing the mainstream perception on the defining role of early oceans. Overall, our results emphasize hydrodynamics as under-represented physical component in existing evolutionary frameworks and generate testable predictions linking organism size, flow conditions, and habitat type.},
}
RevDate: 2026-06-10
Subcellular visualization and quantification of cyanotoxin synthesis in cyanobacteria reveals distinct compartmentation.
Scientific reports, 16(1):.
UNLABELLED: The bloom-forming cyanobacteria Microcystis and Planktothrix produce cyanotoxins such as microcystins (MCs) and anabaenopeptins (APs) through nonribosomal peptide synthesis (NRPS). Close inspection of their synthesis can aid in understanding the biological function of such cyanotoxins. MCs and APs were visualized using chemoselective labeling, and a heterogeneous distribution of fluorescence signals was observed during both time-lapse signal build-up and decline experiments. The formation of rather distinct entities was quantified using advanced imaging analysis, defining modeled entities (ME) with varying intensities but rather stable volumes, numbers and localization. The origin of MC synthesis was mostly in the cytoplasm of unicellular Microcystis and was confirmed through immunolabeling. In contrast, for APs in filamentous Planktothrix, the origin was localized in the membrane region near the septa between filament cells. Our data suggest distinct cyanotoxin biosynthesis centers in cells, differing in their localization between unicellular and multicellular cyanobacteria.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-47303-1.
Additional Links: PMID-42002598
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42002598,
year = {2026},
author = {Morón-Asensio, R and Kurmayer, R},
title = {Subcellular visualization and quantification of cyanotoxin synthesis in cyanobacteria reveals distinct compartmentation.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42002598},
issn = {2045-2322},
support = {P392670//Tiroler Nachwuchsforscher*innenförderung/ ; P32193//Austrian Science Fund/ ; },
abstract = {UNLABELLED: The bloom-forming cyanobacteria Microcystis and Planktothrix produce cyanotoxins such as microcystins (MCs) and anabaenopeptins (APs) through nonribosomal peptide synthesis (NRPS). Close inspection of their synthesis can aid in understanding the biological function of such cyanotoxins. MCs and APs were visualized using chemoselective labeling, and a heterogeneous distribution of fluorescence signals was observed during both time-lapse signal build-up and decline experiments. The formation of rather distinct entities was quantified using advanced imaging analysis, defining modeled entities (ME) with varying intensities but rather stable volumes, numbers and localization. The origin of MC synthesis was mostly in the cytoplasm of unicellular Microcystis and was confirmed through immunolabeling. In contrast, for APs in filamentous Planktothrix, the origin was localized in the membrane region near the septa between filament cells. Our data suggest distinct cyanotoxin biosynthesis centers in cells, differing in their localization between unicellular and multicellular cyanobacteria.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-47303-1.},
}
RevDate: 2026-06-10
Social immunity can be a consequence and cause of social evolution.
Proceedings of the National Academy of Sciences of the United States of America, 123(24):e2518957123.
Many social insects respond to pathogens in ways that reduce pathogen transmission within their social groups, with behaviors such as grooming or removing infected individuals. This "social immunity" within a group has been compared to the immune response of multicellular organisms. However, we lack a theoretical framework for understanding both the possible evolutionary origins and consequences of social immunity. How restrictive are the conditions for the initial evolution of social immunity? Would we expect social immunity to influence or even coevolve with other aspects of social complexity, such as colony size or the number of castes? We developed a theoretical framework for examining the evolutionary scenarios that may link social immunity and social evolution. We found that: (1) social immunity can be favored in relatively simple social systems, where relatedness between group members can vary; (2) social immunity can coevolve with the age of colony maturation, leading to colonies that grow for a longer period before they start reproducing; and (3) social immunity often leads to the evolution of larger colonies, which can then select for more worker castes. These results suggest that social immunity can be both a consequence and a cause of social evolution.
Additional Links: PMID-42268894
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42268894,
year = {2026},
author = {Liu, M and Scott, TW and Shillcock, G and Pull, CD and West, SA},
title = {Social immunity can be a consequence and cause of social evolution.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {24},
pages = {e2518957123},
doi = {10.1073/pnas.2518957123},
pmid = {42268894},
issn = {1091-6490},
support = {787932//EC | Horizon Europe | Excellent Science | HORIZON EUROPE European Research Council (ERC)/ ; 834164//EC | Horizon Europe | Excellent Science | HORIZON EUROPE European Research Council (ERC)/ ; BB/T008784/1//UKRI | Biotechnology and Biological Sciences Research Council (AFRC)/ ; },
abstract = {Many social insects respond to pathogens in ways that reduce pathogen transmission within their social groups, with behaviors such as grooming or removing infected individuals. This "social immunity" within a group has been compared to the immune response of multicellular organisms. However, we lack a theoretical framework for understanding both the possible evolutionary origins and consequences of social immunity. How restrictive are the conditions for the initial evolution of social immunity? Would we expect social immunity to influence or even coevolve with other aspects of social complexity, such as colony size or the number of castes? We developed a theoretical framework for examining the evolutionary scenarios that may link social immunity and social evolution. We found that: (1) social immunity can be favored in relatively simple social systems, where relatedness between group members can vary; (2) social immunity can coevolve with the age of colony maturation, leading to colonies that grow for a longer period before they start reproducing; and (3) social immunity often leads to the evolution of larger colonies, which can then select for more worker castes. These results suggest that social immunity can be both a consequence and a cause of social evolution.},
}
RevDate: 2026-06-10
The neurovascular unit under siege: Molecular mechanisms and potential drug target for cerebral edema.
Pharmacology & therapeutics pii:S0163-7258(26)00095-1 [Epub ahead of print].
Cerebral edema, a life-threatening accumulation of fluid in the brain parenchyma, is a common complication of neurological injuries that leads to elevated intracranial pressure and high mortality. Current mainstay treatments, primarily osmotic therapies offer only transient relief from symptoms without targeting the underlying pathophysiology and are hampered by significant side effects and a high rate of therapeutic refractoriness. Elucidating the precise molecular mechanisms that drive cerebral edema remains a significant challenge, which has critically limited the identification of viable drug targets and the subsequent development of effective interventions. This review reframes cerebral edema as a failure of multicellular communication within the neurovascular unit (NVU). It examines how disrupted NVU components drive the progression of cytotoxic, ionic, and vasogenic edema through interconnected pathways governing intercellular signaling, ion-water coupling, and glymphatic clearance. Finally, emerging therapeutic strategies are evaluated through the lens of NVU-centered pathophysiology, with emphasis on approaches that restore multicellular dialogue and phase-specific interventions informed by the dynamic evolution of cellular dysfunction after injury.
Additional Links: PMID-42269972
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42269972,
year = {2026},
author = {Han, J and Zhang, H and Zhang, Q and Zhou, J and Hu, Y and Chen, X and He, J and Yan, C and Mao, J and Li, Z and Yan, H and Jin, W},
title = {The neurovascular unit under siege: Molecular mechanisms and potential drug target for cerebral edema.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {109068},
doi = {10.1016/j.pharmthera.2026.109068},
pmid = {42269972},
issn = {1879-016X},
abstract = {Cerebral edema, a life-threatening accumulation of fluid in the brain parenchyma, is a common complication of neurological injuries that leads to elevated intracranial pressure and high mortality. Current mainstay treatments, primarily osmotic therapies offer only transient relief from symptoms without targeting the underlying pathophysiology and are hampered by significant side effects and a high rate of therapeutic refractoriness. Elucidating the precise molecular mechanisms that drive cerebral edema remains a significant challenge, which has critically limited the identification of viable drug targets and the subsequent development of effective interventions. This review reframes cerebral edema as a failure of multicellular communication within the neurovascular unit (NVU). It examines how disrupted NVU components drive the progression of cytotoxic, ionic, and vasogenic edema through interconnected pathways governing intercellular signaling, ion-water coupling, and glymphatic clearance. Finally, emerging therapeutic strategies are evaluated through the lens of NVU-centered pathophysiology, with emphasis on approaches that restore multicellular dialogue and phase-specific interventions informed by the dynamic evolution of cellular dysfunction after injury.},
}
RevDate: 2026-06-11
Evaluating the impact of dynamic fluid flow on an advanced model of pancreatic cancer: Towards desmoplasia disruption and chemosensitivity promotion.
Biomaterials advances, 188:214984 pii:S2772-9508(26)00282-7 [Epub ahead of print].
Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly malignancy with a very low survival rate. Asymptomatic disease progression, a complex tumour microenvironment (TME) and high resistance to current therapeutic methods, all contribute towards PDAC's dismal statistics. A key challenge towards better understanding of this deadly disease and its therapeutic response is the development of an in vitro disease model that is capable of mimicking the various complex and important features of the PDAC TME such as the biological/cellular, the biochemical as well as the biomechanical/biophysical complexity. We have previously developed a complex multicellular model of PDAC which is a spatially advanced multicellular scaffold that mimics the desmoplasia of PDAC. In this work, we have elucidated the importance/effect of interstitial fluid flow in the model. More specifically, we incorporated our multicellular PDAC model in a dynamic bioreactor for a flow rate of 3.5 ml/min. We exposed the model to flow either short-term (5 days) or long term (14 days). Thereafter we monitored the evolution of the cells under flow as well as their response to chemotherapy, as compared to non-dynamic (static) culture. Overall, fluid flow promoted the mesenchymal and reduced the epithelial cell population in our model, as compared to static conditions. Furthermore, the duration of the flow impacted the functionality of activated stellate cells, i.e., short-term flow promoted a more fibrotic/desmoplastic phenotype while long-term flow reduced the fibrosis, disrupted the deposition of collagen and increased the inflammatory levels. As a result, short-term flow exposure led to higher chemotherapy resistance as compared to long-term flow. This work highlights how dynamic flow can alter key features of in vitro models as well as the importance of flow consideration for increased in vitro biomimicry.
Additional Links: PMID-42275839
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42275839,
year = {2026},
author = {Gupta, P and Richardson, J and Wilkinson, M and Klymenko, OV and Bakkalci, D and Cheema, U and Kocher, HM and Pérez-Mancera, PA and Velliou, EG},
title = {Evaluating the impact of dynamic fluid flow on an advanced model of pancreatic cancer: Towards desmoplasia disruption and chemosensitivity promotion.},
journal = {Biomaterials advances},
volume = {188},
number = {},
pages = {214984},
doi = {10.1016/j.bioadv.2026.214984},
pmid = {42275839},
issn = {2772-9508},
abstract = {Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly malignancy with a very low survival rate. Asymptomatic disease progression, a complex tumour microenvironment (TME) and high resistance to current therapeutic methods, all contribute towards PDAC's dismal statistics. A key challenge towards better understanding of this deadly disease and its therapeutic response is the development of an in vitro disease model that is capable of mimicking the various complex and important features of the PDAC TME such as the biological/cellular, the biochemical as well as the biomechanical/biophysical complexity. We have previously developed a complex multicellular model of PDAC which is a spatially advanced multicellular scaffold that mimics the desmoplasia of PDAC. In this work, we have elucidated the importance/effect of interstitial fluid flow in the model. More specifically, we incorporated our multicellular PDAC model in a dynamic bioreactor for a flow rate of 3.5 ml/min. We exposed the model to flow either short-term (5 days) or long term (14 days). Thereafter we monitored the evolution of the cells under flow as well as their response to chemotherapy, as compared to non-dynamic (static) culture. Overall, fluid flow promoted the mesenchymal and reduced the epithelial cell population in our model, as compared to static conditions. Furthermore, the duration of the flow impacted the functionality of activated stellate cells, i.e., short-term flow promoted a more fibrotic/desmoplastic phenotype while long-term flow reduced the fibrosis, disrupted the deposition of collagen and increased the inflammatory levels. As a result, short-term flow exposure led to higher chemotherapy resistance as compared to long-term flow. This work highlights how dynamic flow can alter key features of in vitro models as well as the importance of flow consideration for increased in vitro biomimicry.},
}
RevDate: 2026-06-09
The cost of fame for popular species: strong risk of biases in comparative oncology of captive species.
Proceedings. Biological sciences, 293(2072):.
Comparative oncology investigates variation in cancer risk across species by analysing relationships between observed tumour prevalence and factors such as body mass, longevity, life-history traits and mutation rates. These patterns underpin hypotheses on cancer defences, conservation strategies and the evolution of multicellularity, so their robustness is critical. Here, we show that species' scientific and public popularity substantially biases these trends. Reanalysing published captive vertebrate datasets, and re-evaluating previously published trends, we found that controlling for popularity eliminated the weak positive associations previously reported between body mass and both tumour and malignancy prevalence, supporting Peto's paradox. The positive link between germline mutation rate and cancer mortality also disappeared. In birds, the effect of clutch size doubled for species with a large clutch size, while in mammals, tumour prevalence was underestimated in less popular species. Finally, the endotheliochorial placentation-mortality association vanished after accounting for confounders. These findings reveal that species popularity can substantially distort comparative cancer analyses and should be systematically controlled in future studies.
Additional Links: PMID-42264491
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42264491,
year = {2026},
author = {Dujon, AM and Courtalon, J and Asselin, K and Thomas, F},
title = {The cost of fame for popular species: strong risk of biases in comparative oncology of captive species.},
journal = {Proceedings. Biological sciences},
volume = {293},
number = {2072},
pages = {},
doi = {10.1098/rspb.2026.0504},
pmid = {42264491},
issn = {1471-2954},
support = {//Agence Nationale de la Recherche/ ; //CNRS (IRP CANECEV)/ ; //The HOFFMANN Family/ ; },
abstract = {Comparative oncology investigates variation in cancer risk across species by analysing relationships between observed tumour prevalence and factors such as body mass, longevity, life-history traits and mutation rates. These patterns underpin hypotheses on cancer defences, conservation strategies and the evolution of multicellularity, so their robustness is critical. Here, we show that species' scientific and public popularity substantially biases these trends. Reanalysing published captive vertebrate datasets, and re-evaluating previously published trends, we found that controlling for popularity eliminated the weak positive associations previously reported between body mass and both tumour and malignancy prevalence, supporting Peto's paradox. The positive link between germline mutation rate and cancer mortality also disappeared. In birds, the effect of clutch size doubled for species with a large clutch size, while in mammals, tumour prevalence was underestimated in less popular species. Finally, the endotheliochorial placentation-mortality association vanished after accounting for confounders. These findings reveal that species popularity can substantially distort comparative cancer analyses and should be systematically controlled in future studies.},
}
RevDate: 2026-06-09
A unicellular relative links aggregative multicellularity to animal origins.
Nature pii:10.1038/s41586-026-10748-5 [Epub ahead of print].
How animals evolved complex multicellularity from their unicellular ancestors remains unanswered. Unicellular relatives of animals exhibit simple multicellularity through clonal division, formation of multinucleate coenocytes, or aggregation. [1] Therefore, animal multicellularity may have evolved from one (or a combination) of these behaviours. Aggregation has classically been dismissed as a means to complex multicellularity. [2] However, aggregation occurs in many extant animal cells and has also been recently described in three close unicellular relatives of animals (the choanoflagellates Salpingoeca rosetta and Choanoeca flexa, and the filasterean Capsaspora owczarzaki). [3-5] It is unclear whether aggregation in these species is derived or ancestral, and its relevance for animal origins remains unknown. To fill this gap, we investigated whether an additional close unicellular relative of animals can undergo aggregation. We discovered that the marine free-living bacterivorous filasterean Ministeria vibrans [6] forms homogeneous aggregates with reproducible kinetics that have long-term stability, and that improved feeding and mating may be evolutionary drivers of this aggregation. Notably, we found that homologs of many animal multicellularity genes involved in cell adhesion, signalling, and transcriptional regulation were deployed during the aggregation process, indicating that they may have been used for aggregation in the unicellular ancestors of animals before being co-opted into animal multicellular development. Thus, our results imply that aggregative multicellularity was key to the development of the multicellular animal genetic toolkit.
Additional Links: PMID-42265479
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42265479,
year = {2026},
author = {Li, R and Dharamshi, JE and Kwok, K and Ruiz-Trillo, I and Gerdt, JP},
title = {A unicellular relative links aggregative multicellularity to animal origins.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-026-10748-5},
pmid = {42265479},
issn = {1476-4687},
abstract = {How animals evolved complex multicellularity from their unicellular ancestors remains unanswered. Unicellular relatives of animals exhibit simple multicellularity through clonal division, formation of multinucleate coenocytes, or aggregation. [1] Therefore, animal multicellularity may have evolved from one (or a combination) of these behaviours. Aggregation has classically been dismissed as a means to complex multicellularity. [2] However, aggregation occurs in many extant animal cells and has also been recently described in three close unicellular relatives of animals (the choanoflagellates Salpingoeca rosetta and Choanoeca flexa, and the filasterean Capsaspora owczarzaki). [3-5] It is unclear whether aggregation in these species is derived or ancestral, and its relevance for animal origins remains unknown. To fill this gap, we investigated whether an additional close unicellular relative of animals can undergo aggregation. We discovered that the marine free-living bacterivorous filasterean Ministeria vibrans [6] forms homogeneous aggregates with reproducible kinetics that have long-term stability, and that improved feeding and mating may be evolutionary drivers of this aggregation. Notably, we found that homologs of many animal multicellularity genes involved in cell adhesion, signalling, and transcriptional regulation were deployed during the aggregation process, indicating that they may have been used for aggregation in the unicellular ancestors of animals before being co-opted into animal multicellular development. Thus, our results imply that aggregative multicellularity was key to the development of the multicellular animal genetic toolkit.},
}
RevDate: 2026-06-09
Simulating Life, Challenging the Law: Creation and Responsibility in the Governance of Human Embryo Models.
Journal of bioethical inquiry [Epub ahead of print].
Rapid advances in stem cell science have generated stem cell-based embryo models (SCBEMs), multicellular structures derived from pluripotent stem cells that recapitulate key features of early human development without originating from fertilization. Although the literature also refers to these entities as "human embryo models" or "embryoids," this article adopts the term SCBEM to reflect their stem cell derivation and to maintain terminological precision. Originally presented as an alternative research platform to embryos, SCBEMs are increasingly exhibiting embryo-like structural and developmental organization. Their trajectory raises a familiar ethical warning about scientific creation outpacing responsibility and exposes significant gaps in legal definitions that rely on origin-based criteria (fertilization, cloning, parthenogenesis) instead of functional characteristics and demonstrated developmental potential. This article develops a South African-centred analysis within a comparative frame, arguing for a bespoke governance framework that is principled, proportionate, and adaptive. It proposes: (i) revised statutory definitions that are tethered to potential and organization; (ii) specialist oversight and a national register; (iii) a culture-limit policy that is aligned with resemblance (and distinct from the fourteen-day rule which applies in relation to embryos); (iv) bright-line prohibitions on any reproductive use or transfer into human or animal hosts; and (v) mechanisms for public trust, transparency, and cross-border harmonization. The aim is to enable socially valuable research while closing loopholes that could erode ethics oversight and public confidence. This article clarifies the legal-ethical problem through the lenses of potentiality and developmental resemblance, maps the comparative governance of SCBEMs with lessons for South Africa, and offers a model framework which includes definitions, oversight architecture, culture-limit policy, prohibitions, and transparency that are designed to be future-ready. A doctrinal analysis of primary law and authoritative guidance was adopted, supplemented by comparative review and governance design principles (proportionality, accountability, transparency). Where formal sources are silent, policy-ready rules were derived from best-practice codes and ethics literature.
Additional Links: PMID-42262451
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42262451,
year = {2026},
author = {Soni, S},
title = {Simulating Life, Challenging the Law: Creation and Responsibility in the Governance of Human Embryo Models.},
journal = {Journal of bioethical inquiry},
volume = {},
number = {},
pages = {},
pmid = {42262451},
issn = {1872-4353},
abstract = {Rapid advances in stem cell science have generated stem cell-based embryo models (SCBEMs), multicellular structures derived from pluripotent stem cells that recapitulate key features of early human development without originating from fertilization. Although the literature also refers to these entities as "human embryo models" or "embryoids," this article adopts the term SCBEM to reflect their stem cell derivation and to maintain terminological precision. Originally presented as an alternative research platform to embryos, SCBEMs are increasingly exhibiting embryo-like structural and developmental organization. Their trajectory raises a familiar ethical warning about scientific creation outpacing responsibility and exposes significant gaps in legal definitions that rely on origin-based criteria (fertilization, cloning, parthenogenesis) instead of functional characteristics and demonstrated developmental potential. This article develops a South African-centred analysis within a comparative frame, arguing for a bespoke governance framework that is principled, proportionate, and adaptive. It proposes: (i) revised statutory definitions that are tethered to potential and organization; (ii) specialist oversight and a national register; (iii) a culture-limit policy that is aligned with resemblance (and distinct from the fourteen-day rule which applies in relation to embryos); (iv) bright-line prohibitions on any reproductive use or transfer into human or animal hosts; and (v) mechanisms for public trust, transparency, and cross-border harmonization. The aim is to enable socially valuable research while closing loopholes that could erode ethics oversight and public confidence. This article clarifies the legal-ethical problem through the lenses of potentiality and developmental resemblance, maps the comparative governance of SCBEMs with lessons for South Africa, and offers a model framework which includes definitions, oversight architecture, culture-limit policy, prohibitions, and transparency that are designed to be future-ready. A doctrinal analysis of primary law and authoritative guidance was adopted, supplemented by comparative review and governance design principles (proportionality, accountability, transparency). Where formal sources are silent, policy-ready rules were derived from best-practice codes and ethics literature.},
}
RevDate: 2026-06-08
A single-cell blueprint for cellular diversity in the Green Lineage.
Current biology : CB, 36(11):R577-R589.
The Green Lineage (Viridiplantae) represents one of the most successful evolutionary radiations on Earth, with remarkable morphological diversity from unicellular algae to complex multicellular land plants. Recent advances in single-cell genomics have transformed our understanding of plant cell-type diversity and evolution, revealing fundamental principles underlying cellular organization and specification. This review synthesizes current knowledge of plant cell-type identity and evolution through the lens of single-cell approaches. We examine how plant cell types are specified through combinatorial transcription factor networks analogous to animal terminal selector systems yet operate within a fundamentally different developmental framework characterized by positional determination, extensive plasticity, and environmental responsiveness. We highlight unique features of plant cells, including plastids, large vacuoles, cell walls, and plasmodesmata, that profoundly influence cellular identity and present distinct challenges for single-cell profiling. Comparative analysis across the Green Lineage reveals that new cell types arise through subfunctionalization following gene and genome duplications, co-option of ancestral gene regulatory networks, and cis-regulatory evolution driven by transposable elements. We address major analytical challenges, including orthology assignment in polyploid genomes, cross-species dataset integration, gene regulatory network reconstruction, and functional validation in diverse plant systems. Despite these challenges, plant single-cell genomics offers unprecedented opportunities to understand cellular evolution, with implications extending from fundamental biology to agricultural innovation.
Additional Links: PMID-42259272
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42259272,
year = {2026},
author = {Coate, JE and Doyle, JJ and Farmer, A and Huang, SC and Kajala, K and Kenchanmane Raju, SK and Kumari, S and Palfalvi, G and Radin, I and Singh, P and Stata, M and Ware, D and Yao, Q and Nikolov, LA},
title = {A single-cell blueprint for cellular diversity in the Green Lineage.},
journal = {Current biology : CB},
volume = {36},
number = {11},
pages = {R577-R589},
doi = {10.1016/j.cub.2026.04.003},
pmid = {42259272},
issn = {1879-0445},
abstract = {The Green Lineage (Viridiplantae) represents one of the most successful evolutionary radiations on Earth, with remarkable morphological diversity from unicellular algae to complex multicellular land plants. Recent advances in single-cell genomics have transformed our understanding of plant cell-type diversity and evolution, revealing fundamental principles underlying cellular organization and specification. This review synthesizes current knowledge of plant cell-type identity and evolution through the lens of single-cell approaches. We examine how plant cell types are specified through combinatorial transcription factor networks analogous to animal terminal selector systems yet operate within a fundamentally different developmental framework characterized by positional determination, extensive plasticity, and environmental responsiveness. We highlight unique features of plant cells, including plastids, large vacuoles, cell walls, and plasmodesmata, that profoundly influence cellular identity and present distinct challenges for single-cell profiling. Comparative analysis across the Green Lineage reveals that new cell types arise through subfunctionalization following gene and genome duplications, co-option of ancestral gene regulatory networks, and cis-regulatory evolution driven by transposable elements. We address major analytical challenges, including orthology assignment in polyploid genomes, cross-species dataset integration, gene regulatory network reconstruction, and functional validation in diverse plant systems. Despite these challenges, plant single-cell genomics offers unprecedented opportunities to understand cellular evolution, with implications extending from fundamental biology to agricultural innovation.},
}
RevDate: 2026-06-08
Convergent paths to multicellular complexity in photosynthetic eukaryotes.
Current biology : CB, 36(11):R668-R676.
Multicellularity evolved multiple times independently in eukaryotes and has enabled the emergence of complex organisms with various specialized cell types and organs. While principles governing multicellular development are often studied in each domain of life separately, there are clear similarities in shape and form, likely driven by common ecological challenges or physical constraints. We here explore the analogies in multicellular development and its underpinnings in plants and in brown and red algae - photosynthetic multicellular eukaryotes whose last common ancestor was unicellular. We identify conceptual homologies and discuss examples of common underlying genetic, biochemical, and cellular principles, which we hope will inspire more integrated and comparative investigation into the principles that underlie complex multicellularity.
Additional Links: PMID-42259279
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42259279,
year = {2026},
author = {Coelho, SM and Weijers, D},
title = {Convergent paths to multicellular complexity in photosynthetic eukaryotes.},
journal = {Current biology : CB},
volume = {36},
number = {11},
pages = {R668-R676},
doi = {10.1016/j.cub.2026.04.026},
pmid = {42259279},
issn = {1879-0445},
abstract = {Multicellularity evolved multiple times independently in eukaryotes and has enabled the emergence of complex organisms with various specialized cell types and organs. While principles governing multicellular development are often studied in each domain of life separately, there are clear similarities in shape and form, likely driven by common ecological challenges or physical constraints. We here explore the analogies in multicellular development and its underpinnings in plants and in brown and red algae - photosynthetic multicellular eukaryotes whose last common ancestor was unicellular. We identify conceptual homologies and discuss examples of common underlying genetic, biochemical, and cellular principles, which we hope will inspire more integrated and comparative investigation into the principles that underlie complex multicellularity.},
}
RevDate: 2026-06-07
Early evolution of the prokaryotic transcription factor repertoire.
Genome biology and evolution pii:8703513 [Epub ahead of print].
Transcription initiation is regulated by transcription factors (TFs). Though TFs determine phenotype they are nonessential for minimal cellular life. Given this and the idea that it is a certain level of organism 'complexity' that calls for transcription regulation, we traced the evolution of TF repertoire on a bacterio-archaeal phylogeny using a dataset of ∼500,000 TFs. The most ancestral prokaryotes probably encoded multiple TFs. These, based on functions of extant relatives, possibly regulated sugar-fermentation metabolism, sensed overall metabolic state and redox, responded to DNA damage or bound metals; many of which are consistent with some reconstructions of ancestral gene pools and physiologies. The number of TFs and their superfamily-level diversity, through evolutionary history, are similar to those in extant bacteria. These suggest pre-LUCA diversification of TF families. Emergence of new TFs along the phylogeny shows innovation early in prokaryote evolution, in contrast to eukaryotes, in which many TF families emerged in bursts at multicellular lineages. Gains of TFs late in prokaryotic evolution appear to be products of horizontal acquisition of proteins discovered earlier along some other lineage. We speculate on the difference between the evolutionary trajectory of prokaryotic and eukaryotic TF repertoire and how this might be explained by how complexity is envisioned in these two different kingdoms.
Additional Links: PMID-42252092
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42252092,
year = {2026},
author = {Singh, IR and Dubey, A and Seshasayee, ASN},
title = {Early evolution of the prokaryotic transcription factor repertoire.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evag141},
pmid = {42252092},
issn = {1759-6653},
abstract = {Transcription initiation is regulated by transcription factors (TFs). Though TFs determine phenotype they are nonessential for minimal cellular life. Given this and the idea that it is a certain level of organism 'complexity' that calls for transcription regulation, we traced the evolution of TF repertoire on a bacterio-archaeal phylogeny using a dataset of ∼500,000 TFs. The most ancestral prokaryotes probably encoded multiple TFs. These, based on functions of extant relatives, possibly regulated sugar-fermentation metabolism, sensed overall metabolic state and redox, responded to DNA damage or bound metals; many of which are consistent with some reconstructions of ancestral gene pools and physiologies. The number of TFs and their superfamily-level diversity, through evolutionary history, are similar to those in extant bacteria. These suggest pre-LUCA diversification of TF families. Emergence of new TFs along the phylogeny shows innovation early in prokaryote evolution, in contrast to eukaryotes, in which many TF families emerged in bursts at multicellular lineages. Gains of TFs late in prokaryotic evolution appear to be products of horizontal acquisition of proteins discovered earlier along some other lineage. We speculate on the difference between the evolutionary trajectory of prokaryotic and eukaryotic TF repertoire and how this might be explained by how complexity is envisioned in these two different kingdoms.},
}
RevDate: 2026-06-05
CmpDate: 2026-06-05
Inter-individual gene expression variability implies stable regulation of brain-biased genes across organs in three ray-finned fishes.
bioRxiv : the preprint server for biology pii:2024.11.11.623020.
Phenotypic variation among individuals provides the raw material for evolution, and gene expression is a key mediator between genetic and phenotypic variation. As for phenotypes, the range of gene expression is limited and biased by evolutionary and developmental constraints. Observed expression variability due to biomolecular stochasticity and cell-to-cell heterogeneity has been well-studied in isogenic populations of unicellular organisms. However, for multicellular organisms with a diversity of cells and tissues sharing the same genetic background, the interplay between expression variability, gene and organ function, and gene regulation remains an open question. Here, we use highly multiplexed 3'-end bulk RNA sequencing to generate transcriptome profiles spanning at least nine organs in outbred individuals of three ray-finned fish species: zebrafish, Northern pike, and spotted gar. Per organ, we quantify individual-to-individual gene expression variability independent of mean expression level. Lowly variable genes are enriched in cellular housekeeping functions whereas highly variable genes are enriched in stimulus-response functions. Furthermore, highly variable genes evolve under weaker purifying selection at the protein-coding sequence, indicating that intra-species expression variability predicts inter-species protein sequence divergence. Genes that are broadly expressed across organs are both highly expressed and lowly variable, whereas organ-biased genes are typically highly variable within their top organ. Among organ-biased genes, patterns of expression variance are dependent on the top organ. Specifically, brain- and gonads-biased genes have lowly variable expression across different organs, suggesting stabilizing selection. These patterns suggest that gene regulatory mechanisms evolve under organ-specific selective pressures.
Additional Links: PMID-42244546
Full Text:
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42244546,
year = {2026},
author = {Bucao, CF and Aletti, C and Laverré, A and Moretti, S and Trouvé, A and Thompson, AW and Racicot, BL and Wilson, CA and Bobe, J and Braasch, I and Guiguen, Y and Postlethwait, JH and Robinson-Rechavi, M},
title = {Inter-individual gene expression variability implies stable regulation of brain-biased genes across organs in three ray-finned fishes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.11.623020},
pmid = {42244546},
issn = {2692-8205},
abstract = {Phenotypic variation among individuals provides the raw material for evolution, and gene expression is a key mediator between genetic and phenotypic variation. As for phenotypes, the range of gene expression is limited and biased by evolutionary and developmental constraints. Observed expression variability due to biomolecular stochasticity and cell-to-cell heterogeneity has been well-studied in isogenic populations of unicellular organisms. However, for multicellular organisms with a diversity of cells and tissues sharing the same genetic background, the interplay between expression variability, gene and organ function, and gene regulation remains an open question. Here, we use highly multiplexed 3'-end bulk RNA sequencing to generate transcriptome profiles spanning at least nine organs in outbred individuals of three ray-finned fish species: zebrafish, Northern pike, and spotted gar. Per organ, we quantify individual-to-individual gene expression variability independent of mean expression level. Lowly variable genes are enriched in cellular housekeeping functions whereas highly variable genes are enriched in stimulus-response functions. Furthermore, highly variable genes evolve under weaker purifying selection at the protein-coding sequence, indicating that intra-species expression variability predicts inter-species protein sequence divergence. Genes that are broadly expressed across organs are both highly expressed and lowly variable, whereas organ-biased genes are typically highly variable within their top organ. Among organ-biased genes, patterns of expression variance are dependent on the top organ. Specifically, brain- and gonads-biased genes have lowly variable expression across different organs, suggesting stabilizing selection. These patterns suggest that gene regulatory mechanisms evolve under organ-specific selective pressures.},
}
RevDate: 2026-06-04
CmpDate: 2026-06-04
Cell division timing shapes the morphology and size of nascent multicellular organisms.
bioRxiv : the preprint server for biology pii:2025.04.23.650085.
Upon making the transition from unicellularity to multicellularity, many previously optimized cellular traits experience the renewed scrutiny of natural selection due to their novel effects on emergent multicellular phenotypes. Yet we lack a comprehensive understanding of how and why specific cellular traits influence multicellular phenotypes and fitness. The snowflake yeast model system provides a tractable entry point for such investigations. The effects of several cell-level traits (cellular aspect ratio, cell volume, bud neck strength) on multicellular cluster size have been characterized, but we found that these properties were insufficient to explain the difference in cluster size between the two strains that serve as the ancestors of the ongoing Multicellularity Long-Term Evolution Experiment (MuLTEE). Using time-lapse microscopy and single cell tracking, we identified the timing of cell division as a cellular trait that strongly influences multicellular morphology and size in snowflake yeast. The "petite" ancestor divides asynchronously, with a 25% longer first division, while the "grande" ancestor divided synchronously. Using network theoretical and biophysical models, we showed that strains exhibiting a first division delay generate more highly-branched network topologies, accelerating the accumulation of crowding-induced mechanical stress, resulting in clusters that fracture at smaller sizes. Conversely, synchronously dividing strains produce more symmetric, larger clusters. Synchronous cell division can provide benefits through both faster growth and larger size, suggesting multiple potential selective pathways for its evolution. Furthermore, we explore how accelerated first division can produce even larger groups and how another unexpected mechanism for modifying cluster size, apoptosis rate, may interfere with these effects. Our results identify cell division timing as a previously underappreciated axis of phenotypic variation that strongly influences multicellular morphology. This suggests that temporal regulation of cell division represents an evolutionarily accessible mechanism for early control of morphogenesis in nascent multicellular organisms with permanent intercellular bonds.
Additional Links: PMID-42239451
Full Text:
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42239451,
year = {2026},
author = {Cedeño-Pérez, LF and Pineau, RM and Day, TC and Ratcliff, WC and Conlin, PL},
title = {Cell division timing shapes the morphology and size of nascent multicellular organisms.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.23.650085},
pmid = {42239451},
issn = {2692-8205},
abstract = {Upon making the transition from unicellularity to multicellularity, many previously optimized cellular traits experience the renewed scrutiny of natural selection due to their novel effects on emergent multicellular phenotypes. Yet we lack a comprehensive understanding of how and why specific cellular traits influence multicellular phenotypes and fitness. The snowflake yeast model system provides a tractable entry point for such investigations. The effects of several cell-level traits (cellular aspect ratio, cell volume, bud neck strength) on multicellular cluster size have been characterized, but we found that these properties were insufficient to explain the difference in cluster size between the two strains that serve as the ancestors of the ongoing Multicellularity Long-Term Evolution Experiment (MuLTEE). Using time-lapse microscopy and single cell tracking, we identified the timing of cell division as a cellular trait that strongly influences multicellular morphology and size in snowflake yeast. The "petite" ancestor divides asynchronously, with a 25% longer first division, while the "grande" ancestor divided synchronously. Using network theoretical and biophysical models, we showed that strains exhibiting a first division delay generate more highly-branched network topologies, accelerating the accumulation of crowding-induced mechanical stress, resulting in clusters that fracture at smaller sizes. Conversely, synchronously dividing strains produce more symmetric, larger clusters. Synchronous cell division can provide benefits through both faster growth and larger size, suggesting multiple potential selective pathways for its evolution. Furthermore, we explore how accelerated first division can produce even larger groups and how another unexpected mechanism for modifying cluster size, apoptosis rate, may interfere with these effects. Our results identify cell division timing as a previously underappreciated axis of phenotypic variation that strongly influences multicellular morphology. This suggests that temporal regulation of cell division represents an evolutionarily accessible mechanism for early control of morphogenesis in nascent multicellular organisms with permanent intercellular bonds.},
}
RevDate: 2026-06-04
Inhibition of Sclerostin Protected Against Particle-Induced Osteolysis via Activation of Wnt Signaling and Suppression of Osteoclast Function.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 44(6):e70231.
Periprosthetic osteolysis induced by wear debris remains a leading cause of aseptic loosening after joint arthroplasty, with no established pharmacological treatment. We investigated an anti-sclerostin antibody (Ab-Scl) and elucidated its mechanism of action in cobalt-chromium (CoCr) particle-induced osteolysis. Tartrate-resistant acid phosphatase (TRAP)-tdTomato mice with labeled mature osteoclasts (mOCs) were used. CoCr particles were applied to the calvarial bone, with or without Ab-Scl administration. Intravital two-photon bone imaging, microcomputed tomography (μCT), and histological and immunohistochemical analyses were performed to evaluate osteolysis, osteoclast activity, and β-catenin expression. In vitro assays using RAW264.7-derived osteoclast-like cells were conducted to investigate downstream signaling pathways. μCT analysis revealed that CoCr particles reduced the bone volume-to-tissue volume fraction and trabecular thickness while increasing trabecular separation and the structural model index; conversely, Ab-Scl significantly attenuated osteolytic changes. Histological analysis showed that CoCr exposure increased the eroded surface area and number of TRAP-positive osteoclasts, both of which were significantly decreased by Ab-Scl. Immunohistochemistry demonstrated that CoCr exposure suppressed β-catenin expression on the bone surface, which was restored by Ab-Scl. Intravital two-photon microscopy revealed that CoCr particles reduced mOC motility and increased the acidic resorptive area, whereas Ab-Scl reversed these changes, enhancing motility and suppressing bone resorption. In vitro, RSPO2 enhanced osteoclastic bone resorption, pit formation, and Pyk2 phosphorylation, which were suppressed by PF-562271. Ab-Scl modulated osteoclast function through Wnt/β-catenin-related mechanisms, potentially involving Pyk2-related pathways, thereby suppressing CoCr particle-induced osteolysis. These findings suggest that Ab-Scl is a promising pharmacological strategy for preventing aseptic loosening following joint arthroplasty.
Additional Links: PMID-42243060
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42243060,
year = {2026},
author = {Ido, H and Takegami, Y and Osawa, Y and Funahashi, H and Otaka, K and Tanaka, S and Oono, K and Nakashima, H and Wake, H and Imagama, S},
title = {Inhibition of Sclerostin Protected Against Particle-Induced Osteolysis via Activation of Wnt Signaling and Suppression of Osteoclast Function.},
journal = {Journal of orthopaedic research : official publication of the Orthopaedic Research Society},
volume = {44},
number = {6},
pages = {e70231},
doi = {10.1002/jor.70231},
pmid = {42243060},
issn = {1554-527X},
support = {//Hori Sciences and Arts Foundation/ ; //Nasu Research Grant/ ; 26K12172//JSPS KAKENHI/ ; },
abstract = {Periprosthetic osteolysis induced by wear debris remains a leading cause of aseptic loosening after joint arthroplasty, with no established pharmacological treatment. We investigated an anti-sclerostin antibody (Ab-Scl) and elucidated its mechanism of action in cobalt-chromium (CoCr) particle-induced osteolysis. Tartrate-resistant acid phosphatase (TRAP)-tdTomato mice with labeled mature osteoclasts (mOCs) were used. CoCr particles were applied to the calvarial bone, with or without Ab-Scl administration. Intravital two-photon bone imaging, microcomputed tomography (μCT), and histological and immunohistochemical analyses were performed to evaluate osteolysis, osteoclast activity, and β-catenin expression. In vitro assays using RAW264.7-derived osteoclast-like cells were conducted to investigate downstream signaling pathways. μCT analysis revealed that CoCr particles reduced the bone volume-to-tissue volume fraction and trabecular thickness while increasing trabecular separation and the structural model index; conversely, Ab-Scl significantly attenuated osteolytic changes. Histological analysis showed that CoCr exposure increased the eroded surface area and number of TRAP-positive osteoclasts, both of which were significantly decreased by Ab-Scl. Immunohistochemistry demonstrated that CoCr exposure suppressed β-catenin expression on the bone surface, which was restored by Ab-Scl. Intravital two-photon microscopy revealed that CoCr particles reduced mOC motility and increased the acidic resorptive area, whereas Ab-Scl reversed these changes, enhancing motility and suppressing bone resorption. In vitro, RSPO2 enhanced osteoclastic bone resorption, pit formation, and Pyk2 phosphorylation, which were suppressed by PF-562271. Ab-Scl modulated osteoclast function through Wnt/β-catenin-related mechanisms, potentially involving Pyk2-related pathways, thereby suppressing CoCr particle-induced osteolysis. These findings suggest that Ab-Scl is a promising pharmacological strategy for preventing aseptic loosening following joint arthroplasty.},
}
RevDate: 2026-06-03
Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein.
PLoS genetics, 22(6):e1012175 pii:PGENETICS-D-25-01120 [Epub ahead of print].
Intramolecular epistasis is increasingly recognized as a key factor shaping patterns of evolutionary rate variation among protein sites and constraining adaptive evolution. While genome-wide analyses have revealed that intramolecular epistatic interactions can drive the spatial clustering of amino acid substitutions, direct empirical evidence for such interactions and their evolutionary consequences remains limited. Using a population genetic screen for spatially-clustered and lineage-specific adaptive amino acid substitutions in Drosophila proteins, we systematically identify experimentally tractable candidates for functional analysis. As proof of concept, we focus on the Trio protein, a Rho guanine nucleotide exchange factor that exhibits three spatially-clustered putatively adaptive amino acid substitutions in the D. melanogaster lineage. By systematically reconstructing evolutionary intermediates in vivo using genome editing, we find that all possible intermediate states exhibit reduced viability and/or locomotor defects, providing strong evidence for epistatic constraints on evolutionary trajectories. Notably, these deleterious effects are recessive, suggesting that intermediate combinations of epistatically interacting amino acid substitutions can accumulate in heterozygotes prior to fixation, thereby circumventing apparent constraints imposed by maladaptive intermediate states. Together, these findings provide a rare empirical view of the fitness landscape shaped by intramolecular epistasis and establish a framework for investigating the constraints on adaptive protein evolution in diploid multicellular organisms.
Additional Links: PMID-42234705
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42234705,
year = {2026},
author = {Borne, F and Taverner, AM and Andolfatto, P},
title = {Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein.},
journal = {PLoS genetics},
volume = {22},
number = {6},
pages = {e1012175},
doi = {10.1371/journal.pgen.1012175},
pmid = {42234705},
issn = {1553-7404},
abstract = {Intramolecular epistasis is increasingly recognized as a key factor shaping patterns of evolutionary rate variation among protein sites and constraining adaptive evolution. While genome-wide analyses have revealed that intramolecular epistatic interactions can drive the spatial clustering of amino acid substitutions, direct empirical evidence for such interactions and their evolutionary consequences remains limited. Using a population genetic screen for spatially-clustered and lineage-specific adaptive amino acid substitutions in Drosophila proteins, we systematically identify experimentally tractable candidates for functional analysis. As proof of concept, we focus on the Trio protein, a Rho guanine nucleotide exchange factor that exhibits three spatially-clustered putatively adaptive amino acid substitutions in the D. melanogaster lineage. By systematically reconstructing evolutionary intermediates in vivo using genome editing, we find that all possible intermediate states exhibit reduced viability and/or locomotor defects, providing strong evidence for epistatic constraints on evolutionary trajectories. Notably, these deleterious effects are recessive, suggesting that intermediate combinations of epistatically interacting amino acid substitutions can accumulate in heterozygotes prior to fixation, thereby circumventing apparent constraints imposed by maladaptive intermediate states. Together, these findings provide a rare empirical view of the fitness landscape shaped by intramolecular epistasis and establish a framework for investigating the constraints on adaptive protein evolution in diploid multicellular organisms.},
}
RevDate: 2026-06-03
Profiling of extracellular vesicles from primary hepatocytes, organoids, and mash patients identifies cell injury-specific signatures.
Scientific reports, 16(1):.
Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a severe form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), traditionally diagnosed via invasive biopsy, underscoring the need for non-invasive alternatives. This study identifies biologically relevant extracellular vesicle (EV) protein signatures associated with MASH using patient serum, primary human hepatocytes (PHH), and human liver organoids (HLO). These complementary models capture distinct aspects of disease progression-circulating EV profiles in patients, hepatic cellular responses in PHH, and multicellular interactions in HLO-providing a comprehensive view of MASH pathophysiology. Using aptamer-based technology, we assayed 6596 proteins from 38 individuals with histological confirmed MASLD and in vitro models. EVs were characterized using nano-flow cytometry, ExoView, and high-resolution microscopy (ONI), with liver-specific markers confirming their origin. Key proteins, including SLC27A5, HP, and CXCL7, were elevated in patient samples, while PHH and HLO models exhibited upregulation of ASGPR1, HP, and CXCL7 under MASH conditions. Proteomic analysis revealed shared pathways across models, with machine learning models achieving AUROC values of 0.97, supporting the diagnostic potential of these protein signatures. This integrative approach advances MASH biomarker discovery by linking localized liver dysfunction with systemic disease mechanisms. These findings highlight clinically relevant EV protein signatures that support the development of non-invasive diagnostics and personalized treatment strategies, including prediction of outcomes for bariatric surgery patients.
Additional Links: PMID-42236744
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42236744,
year = {2026},
author = {Leszczynska, A and Kaufmann, B and Sung, H and Stoess, C and Reca, A and Kim, A and Choi, YK and Tran, C and Kim, SE and Povero, D and Wolfe, B and Crafts, T and Eguchi, A and Feldstein, AE},
title = {Profiling of extracellular vesicles from primary hepatocytes, organoids, and mash patients identifies cell injury-specific signatures.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42236744},
issn = {2045-2322},
support = {113592//DK/ ; 024206//AA/ ; },
abstract = {Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a severe form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), traditionally diagnosed via invasive biopsy, underscoring the need for non-invasive alternatives. This study identifies biologically relevant extracellular vesicle (EV) protein signatures associated with MASH using patient serum, primary human hepatocytes (PHH), and human liver organoids (HLO). These complementary models capture distinct aspects of disease progression-circulating EV profiles in patients, hepatic cellular responses in PHH, and multicellular interactions in HLO-providing a comprehensive view of MASH pathophysiology. Using aptamer-based technology, we assayed 6596 proteins from 38 individuals with histological confirmed MASLD and in vitro models. EVs were characterized using nano-flow cytometry, ExoView, and high-resolution microscopy (ONI), with liver-specific markers confirming their origin. Key proteins, including SLC27A5, HP, and CXCL7, were elevated in patient samples, while PHH and HLO models exhibited upregulation of ASGPR1, HP, and CXCL7 under MASH conditions. Proteomic analysis revealed shared pathways across models, with machine learning models achieving AUROC values of 0.97, supporting the diagnostic potential of these protein signatures. This integrative approach advances MASH biomarker discovery by linking localized liver dysfunction with systemic disease mechanisms. These findings highlight clinically relevant EV protein signatures that support the development of non-invasive diagnostics and personalized treatment strategies, including prediction of outcomes for bariatric surgery patients.},
}
RevDate: 2026-06-02
Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.
Stem cell research & therapy pii:10.1186/s13287-026-05080-8 [Epub ahead of print].
Physiologically relevant liver models are essential for advancing hepatic disorder research, especially for disease modeling and drug development, yet current in vitro systems fail to adequately recapitulate the architecture and function of the liver. Owing to the accessibility, robust proliferation and multilineage differentiation potential of human induced pluripotent stem cells (iPSCs), liver organoids derived from iPSCs have emerged as a promising resource in hepatology. Despite this promise, the field still faces persistent bottlenecks including incomplete hepatic maturation, insufficient incorporation of non-parenchymal cells (notably immune and stromal populations), phenotypic instability, and a lack of consensus on standardized differentiation protocols. Therefore, this review systematically analyzes the challenges and strategies of iPSC differentiation into liver organoids and the related influencing factors by focusing on multidimensional regulation of hepatobiliary development as well as the effects of cellular origin, culture system and liver microenvironment on hepatic differentiation of iPSCs. Moving forward, priority should be given to the following directions: (1) Elucidating the self-assembly mechanism of liver organoids to enable precise control of hepatobiliary differentiation, thereby better governing organoid morphology and improving reproducibility; (2) Replacing exogenous cytokines with small-molecule compounds at different stages of iPSC differentiation to simplify and standardize differentiation protocols; (3) Advancing liver organoid transplantation as a means to validate physiological functionality and shift cell therapy from passive replacement toward active tissue reconstruction; (4) Integrating artificial intelligence to achieve intelligent and precise regulation of hepatic differentiation.
Additional Links: PMID-42226068
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42226068,
year = {2026},
author = {Wu, YH and Wang, Y and Zhang, WJ and Yuan, LL and Chen, Y},
title = {Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-05080-8},
pmid = {42226068},
issn = {1757-6512},
support = {LHZSZ24C200001//Key Project of the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China/ ; 2018YFA0108403//National Key R&D Program of China/ ; },
abstract = {Physiologically relevant liver models are essential for advancing hepatic disorder research, especially for disease modeling and drug development, yet current in vitro systems fail to adequately recapitulate the architecture and function of the liver. Owing to the accessibility, robust proliferation and multilineage differentiation potential of human induced pluripotent stem cells (iPSCs), liver organoids derived from iPSCs have emerged as a promising resource in hepatology. Despite this promise, the field still faces persistent bottlenecks including incomplete hepatic maturation, insufficient incorporation of non-parenchymal cells (notably immune and stromal populations), phenotypic instability, and a lack of consensus on standardized differentiation protocols. Therefore, this review systematically analyzes the challenges and strategies of iPSC differentiation into liver organoids and the related influencing factors by focusing on multidimensional regulation of hepatobiliary development as well as the effects of cellular origin, culture system and liver microenvironment on hepatic differentiation of iPSCs. Moving forward, priority should be given to the following directions: (1) Elucidating the self-assembly mechanism of liver organoids to enable precise control of hepatobiliary differentiation, thereby better governing organoid morphology and improving reproducibility; (2) Replacing exogenous cytokines with small-molecule compounds at different stages of iPSC differentiation to simplify and standardize differentiation protocols; (3) Advancing liver organoid transplantation as a means to validate physiological functionality and shift cell therapy from passive replacement toward active tissue reconstruction; (4) Integrating artificial intelligence to achieve intelligent and precise regulation of hepatic differentiation.},
}
RevDate: 2026-06-01
Decoding the origins of cellular self-organization for engineered biology.
Nature biotechnology [Epub ahead of print].
Cellular self-organization reflects an evolutionary leap in which multicellular coordination became essential. Driven by fundamental constraints like oxygen and nutrient transport, physical laws generate inevitable collective behaviors such as cavitation, folding and branching. These behaviors couple mechanics, signaling and gene regulation to build tissues and organs with spatiotemporal precision through the iterative layering of simple rules. Stem cell-based models of embryogenesis and organogenesis make these principles experimentally tractable, revealing canonical developmental routes and alternative trajectories and failure modes that expose bottlenecks and constraints. In this Perspective, we trace self-organization from evolutionary origins to biophysical inevitability and discuss how emerging tools in stem cell biology and bioengineering are beginning to translate these insights into regenerative strategies. Decoding the rules of morphogenesis will open possibilities to reimagine, simulate and rationally engineer the architecture of living tissues.
Additional Links: PMID-42225946
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42225946,
year = {2026},
author = {Chen, Q and Zernicka-Goetz, M},
title = {Decoding the origins of cellular self-organization for engineered biology.},
journal = {Nature biotechnology},
volume = {},
number = {},
pages = {},
pmid = {42225946},
issn = {1546-1696},
abstract = {Cellular self-organization reflects an evolutionary leap in which multicellular coordination became essential. Driven by fundamental constraints like oxygen and nutrient transport, physical laws generate inevitable collective behaviors such as cavitation, folding and branching. These behaviors couple mechanics, signaling and gene regulation to build tissues and organs with spatiotemporal precision through the iterative layering of simple rules. Stem cell-based models of embryogenesis and organogenesis make these principles experimentally tractable, revealing canonical developmental routes and alternative trajectories and failure modes that expose bottlenecks and constraints. In this Perspective, we trace self-organization from evolutionary origins to biophysical inevitability and discuss how emerging tools in stem cell biology and bioengineering are beginning to translate these insights into regenerative strategies. Decoding the rules of morphogenesis will open possibilities to reimagine, simulate and rationally engineer the architecture of living tissues.},
}
RevDate: 2026-05-31
Exosomal lncRNAs as molecular switches driving macrophage-tumor co-evolution in breast cancer.
Clinical and experimental medicine pii:10.1007/s10238-026-02199-z [Epub ahead of print].
Breast cancer progression is increasingly recognized as a dynamic process shaped by reciprocal communication between malignant cells and the tumor microenvironment (TME). Among immune-cell populations, tumor-associated macrophages (TAMs) are major regulators of immune suppression, metabolic adaptation, angiogenesis, and therapeutic resistance. Emerging evidence indicates that extracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) constitutes an important mechanism underlying tumor-immune communication in breast cancer. In this review, we summarize mechanistically characterized studies examining how exosomal lncRNAs regulate bidirectional signaling between breast cancer cells and macrophages and contribute to tumor progression, immune remodeling, and resistance-associated phenotypes. Tumor-derived exosomal lncRNAs modulate macrophage signaling through pathways associated with signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta (TGF-β), Hippo/Yes-associated protein (YAP), hypoxia-responsive signaling, and autophagy-related remodeling, thereby promoting immunoregulatory and tumor-supportive macrophage phenotypes. Conversely, macrophage-derived exosomal lncRNAs, including hypoxia-inducible factor-1 alpha (HIF-1α)-stabilizing long non-coding RNA (HISLA), reinforce glycolytic adaptation, epithelial-mesenchymal transition, epigenetic remodeling, metastatic plasticity, and resistance to therapy in recipient tumor cells. Exosomal lncRNA signaling additionally influences γδ T cells, endothelial cells, and stromal compartments, supporting broader multicellular regulation within the TME. Collectively, current evidence supports exosomal lncRNAs as biologically important mediators of tumor-immune adaptation in breast cancer. We further discuss the translational potential of circulating exosomal lncRNAs as minimally invasive biomarkers and evaluate therapeutic strategies targeting EV biogenesis, vesicle trafficking, and oncogenic lncRNA cargo molecules. Finally, we highlight current limitations involving EV heterogeneity, lncRNA stoichiometry, and incomplete in vivo validation that remain critical barriers to clinical translation.
Additional Links: PMID-42218707
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42218707,
year = {2026},
author = {Javadian, M and Zeinali, T and Rajabi, M and Mehrasa, Z and Boogari, M and Ramezani, F and Samaeinasab, S and Mahmoudi, Z and Hakimi, H and Sabzehban, R and Najafi, K and Esmaeili, K and Khaksarhaghani, Z and Tahmasebi, S and Rezaei, R},
title = {Exosomal lncRNAs as molecular switches driving macrophage-tumor co-evolution in breast cancer.},
journal = {Clinical and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10238-026-02199-z},
pmid = {42218707},
issn = {1591-9528},
abstract = {Breast cancer progression is increasingly recognized as a dynamic process shaped by reciprocal communication between malignant cells and the tumor microenvironment (TME). Among immune-cell populations, tumor-associated macrophages (TAMs) are major regulators of immune suppression, metabolic adaptation, angiogenesis, and therapeutic resistance. Emerging evidence indicates that extracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) constitutes an important mechanism underlying tumor-immune communication in breast cancer. In this review, we summarize mechanistically characterized studies examining how exosomal lncRNAs regulate bidirectional signaling between breast cancer cells and macrophages and contribute to tumor progression, immune remodeling, and resistance-associated phenotypes. Tumor-derived exosomal lncRNAs modulate macrophage signaling through pathways associated with signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta (TGF-β), Hippo/Yes-associated protein (YAP), hypoxia-responsive signaling, and autophagy-related remodeling, thereby promoting immunoregulatory and tumor-supportive macrophage phenotypes. Conversely, macrophage-derived exosomal lncRNAs, including hypoxia-inducible factor-1 alpha (HIF-1α)-stabilizing long non-coding RNA (HISLA), reinforce glycolytic adaptation, epithelial-mesenchymal transition, epigenetic remodeling, metastatic plasticity, and resistance to therapy in recipient tumor cells. Exosomal lncRNA signaling additionally influences γδ T cells, endothelial cells, and stromal compartments, supporting broader multicellular regulation within the TME. Collectively, current evidence supports exosomal lncRNAs as biologically important mediators of tumor-immune adaptation in breast cancer. We further discuss the translational potential of circulating exosomal lncRNAs as minimally invasive biomarkers and evaluate therapeutic strategies targeting EV biogenesis, vesicle trafficking, and oncogenic lncRNA cargo molecules. Finally, we highlight current limitations involving EV heterogeneity, lncRNA stoichiometry, and incomplete in vivo validation that remain critical barriers to clinical translation.},
}
RevDate: 2026-05-28
CmpDate: 2026-05-28
Animals have expanded the evolutionary legacy of unicellular ancestors in blood cells.
Proceedings of the National Academy of Sciences of the United States of America, 123(23):e2528110123.
Blood cells are common and unique to animals, enabling them to address critical challenges of defense and transport. Thus, their evolution represents a defining innovation in metazoan multicellular life. However, their evolutionary trajectory about how blood cells emerged and diversified throughout animal history remains unclear. Here, we present a combination of bioinformatics and functional data that demonstrate that the metazoan blood cell program most likely originated through the repurposing of an ancestral premetazoan toolkit governed by Fos. This primordial program established the macrophage-like initial blood cells at the metazoan root. Then, the first lineage bifurcation at the origin of Bilateria drove the emergence of a specialized mast/killer lineage, characterized by acquisition of granular proteases for antiparasitic defense. Subsequent deuterostome/vertebrate innovations branched T/NK and erythrocyte/thrombocyte lineages from mast cells while B cells derived from macrophages. Our data also show that a prototypic thymus formed at the gill edges of a chordate ancestor. In line with the evolutionary history, the modern hematopoietic pathway shows a vestige of the phylogeny; differentiation potentials of phylogenetically old cell lineages expressing Fos such as macrophages and mast cells are widely retained, and ancient HSCs with limited lineage potentials have been inherited as origo-lineage progenitors. Our framework provides the history of blood cells showing an adaptive innovation built upon ancient unicellular foundations.
Additional Links: PMID-42207871
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42207871,
year = {2026},
author = {Nagahata, Y and Nishimura, Y and Kaitani, R and Leong, JCK and Oda-Ishii, I and Kohtsuka, H and Abe, S and Ishida, T and Carmona-Rivas, M and Najle, SR and Casacuberta, E and Ikuta, K and Miura, T and Ogasawara, M and Irie, N and Satou, Y and Ruiz-Trillo, I and Kawamoto, H},
title = {Animals have expanded the evolutionary legacy of unicellular ancestors in blood cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {23},
pages = {e2528110123},
doi = {10.1073/pnas.2528110123},
pmid = {42207871},
issn = {1091-6490},
support = {JP 23K15324//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP 202460347//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP 19H05747//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; The Cooperative Research Program 2022//Kyoto University/ ; LiMe Office of Director's Research Grants 2022 (No. 6)//Kyoto University/ ; LiMe Office of Director's Research Grants 2023 (No. 7)//Kyoto University/ ; PID2023-153273NB-I00//Ministerio de Ciencia, Innovación y Universidades (MCIU)/ ; exp. 2021 SGR 00751//Generalitat de Catalunya (Government of Catalonia)/ ; PIE-202120E047- Conexiones-Life//Consejo Superior de Investigaciones Científicas (CSIC)/ ; RYC2023-0 45787-I//MICIU/AEI/10.13039/501100011033 and FSE+ (Spain)/ ; },
mesh = {Animals ; *Biological Evolution ; Phylogeny ; *Blood Cells/cytology/metabolism ; Cell Lineage ; Mast Cells/cytology ; Macrophages/cytology ; Cell Differentiation ; },
abstract = {Blood cells are common and unique to animals, enabling them to address critical challenges of defense and transport. Thus, their evolution represents a defining innovation in metazoan multicellular life. However, their evolutionary trajectory about how blood cells emerged and diversified throughout animal history remains unclear. Here, we present a combination of bioinformatics and functional data that demonstrate that the metazoan blood cell program most likely originated through the repurposing of an ancestral premetazoan toolkit governed by Fos. This primordial program established the macrophage-like initial blood cells at the metazoan root. Then, the first lineage bifurcation at the origin of Bilateria drove the emergence of a specialized mast/killer lineage, characterized by acquisition of granular proteases for antiparasitic defense. Subsequent deuterostome/vertebrate innovations branched T/NK and erythrocyte/thrombocyte lineages from mast cells while B cells derived from macrophages. Our data also show that a prototypic thymus formed at the gill edges of a chordate ancestor. In line with the evolutionary history, the modern hematopoietic pathway shows a vestige of the phylogeny; differentiation potentials of phylogenetically old cell lineages expressing Fos such as macrophages and mast cells are widely retained, and ancient HSCs with limited lineage potentials have been inherited as origo-lineage progenitors. Our framework provides the history of blood cells showing an adaptive innovation built upon ancient unicellular foundations.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Biological Evolution
Phylogeny
*Blood Cells/cytology/metabolism
Cell Lineage
Mast Cells/cytology
Macrophages/cytology
Cell Differentiation
RevDate: 2026-05-25
Streptophyte algae and terrestrialization: breaking down the fundamental challenges from an ECM perspective.
Plant physiology pii:8692881 [Epub ahead of print].
The successful conquest of land by ancient streptophyte algae is closely related to the structural features and functional roles of their extracellular matrix and associated evolutionary innovations. Terrestrialization 500+ million years ago required adaptation to multiple and novel abiotic and biotic stressors. The establishment of a sessile habit which encompasses adhesion likely required special cell surface components like arabinogalactan protein-like macromolecules. The secretion of polysaccharide-rich extracellular polymeric substance (EPS) provided multiple services including establishment of a platform for interactions with surrounding microorganisms, i.e., biofilms. Protection against harmful UV radiation likely included production of phenolic compounds, cuticular components and sporopollenin. Innovations to the various components of the cell wall contributed to the evolution of multicellularity and large thallus sizes, water retention, defense, wound response and interactions with surrounding microorganisms. Yet we are only in an infancy stage in understanding how specific cell wall components contributed to the invasion of land by streptophyte algae. Future studies are needed that encompass much larger taxonomic screening, detailed glycomics and proteomics, mining of biosynthetic pathways and comprehensive analyses of cell wall integrity especially in response to abiotic and biotic stressors of terrestrial habitats.
Additional Links: PMID-42184981
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42184981,
year = {2026},
author = {Domozych, DS},
title = {Streptophyte algae and terrestrialization: breaking down the fundamental challenges from an ECM perspective.},
journal = {Plant physiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/plphys/kiag307},
pmid = {42184981},
issn = {1532-2548},
abstract = {The successful conquest of land by ancient streptophyte algae is closely related to the structural features and functional roles of their extracellular matrix and associated evolutionary innovations. Terrestrialization 500+ million years ago required adaptation to multiple and novel abiotic and biotic stressors. The establishment of a sessile habit which encompasses adhesion likely required special cell surface components like arabinogalactan protein-like macromolecules. The secretion of polysaccharide-rich extracellular polymeric substance (EPS) provided multiple services including establishment of a platform for interactions with surrounding microorganisms, i.e., biofilms. Protection against harmful UV radiation likely included production of phenolic compounds, cuticular components and sporopollenin. Innovations to the various components of the cell wall contributed to the evolution of multicellularity and large thallus sizes, water retention, defense, wound response and interactions with surrounding microorganisms. Yet we are only in an infancy stage in understanding how specific cell wall components contributed to the invasion of land by streptophyte algae. Future studies are needed that encompass much larger taxonomic screening, detailed glycomics and proteomics, mining of biosynthetic pathways and comprehensive analyses of cell wall integrity especially in response to abiotic and biotic stressors of terrestrial habitats.},
}
RevDate: 2026-05-22
CmpDate: 2026-05-22
Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.
Cancer chemotherapy and pharmacology, 96(1):.
BOLD-100, a ruthenium(III) prodrug also known as KP1339, is currently under clinical investigation for its suitability as a co-therapeutic anticancer drug. Unlike platinum-based chemotherapeutics, it has unique non-DNA targets, mainly GRP78, an enzyme responsible for signaling related to protein folding in the ER. Inhibition of this key mediator of the "unfolded protein response" may lead to cell death eventually. The purpose of this study was to assess in vitro the impact of BOLD-100 combinations with oxaliplatin, 5-FU, cisplatin or SN38 in multicellular tumor spheroids (MCTSs) compared to single-drug treatments. Gastric (MKN45, NCI-N87) and colorectal cancer (HCT116, HT29) cell lines were chosen, corresponding to the clinical trial in which patients with tumors of these origins are being treated. Biological effects investigated in this study include cytotoxic activity, synergism/antagonism based on Chou and Talalay's algorithm, formation of reactive oxygen species (ROS) and induction of apoptosis and necrosis. Cytotoxicity tests showed vastly different chemosensitivities in MCTSs of the same tumor origin. In both tumor entities, partially synergistic effects were revealed when BOLD-100 was combined with the drugs mentioned above. The DCFH-DA assay suggested consistent increases of ROS levels after treatment with oxaliplatin and, with restrictions, its combination with BOLD-100. Apoptosis and necrosis were induced in the spheroid models by single-drug and combined treatment, with no hints at antagonism in the combination settings. In conclusion, these findings emphasize the potential of BOLD-100 for combination therapy of gastric and colorectal cancers.
Additional Links: PMID-42171754
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42171754,
year = {2026},
author = {Wenisch, D and Ždravac, S and Jakupec, MA and Jirsa, F and Keppler, BK},
title = {Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.},
journal = {Cancer chemotherapy and pharmacology},
volume = {96},
number = {1},
pages = {},
pmid = {42171754},
issn = {1432-0843},
mesh = {Humans ; *Spheroids, Cellular/drug effects ; *Antineoplastic Combined Chemotherapy Protocols/pharmacology/administration & dosage ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Drug Synergism ; Oxaliplatin ; Endoplasmic Reticulum Chaperone BiP ; Cell Line, Tumor ; HT29 Cells ; Fluorouracil/administration & dosage/pharmacology ; Cisplatin/administration & dosage/pharmacology ; HCT116 Cells ; Organoplatinum Compounds/administration & dosage/pharmacology ; Irinotecan ; *Gastrointestinal Neoplasms/drug therapy/pathology ; *Organometallic Compounds/pharmacology/administration & dosage ; *Stomach Neoplasms/drug therapy/pathology ; Antineoplastic Agents/pharmacology ; },
abstract = {BOLD-100, a ruthenium(III) prodrug also known as KP1339, is currently under clinical investigation for its suitability as a co-therapeutic anticancer drug. Unlike platinum-based chemotherapeutics, it has unique non-DNA targets, mainly GRP78, an enzyme responsible for signaling related to protein folding in the ER. Inhibition of this key mediator of the "unfolded protein response" may lead to cell death eventually. The purpose of this study was to assess in vitro the impact of BOLD-100 combinations with oxaliplatin, 5-FU, cisplatin or SN38 in multicellular tumor spheroids (MCTSs) compared to single-drug treatments. Gastric (MKN45, NCI-N87) and colorectal cancer (HCT116, HT29) cell lines were chosen, corresponding to the clinical trial in which patients with tumors of these origins are being treated. Biological effects investigated in this study include cytotoxic activity, synergism/antagonism based on Chou and Talalay's algorithm, formation of reactive oxygen species (ROS) and induction of apoptosis and necrosis. Cytotoxicity tests showed vastly different chemosensitivities in MCTSs of the same tumor origin. In both tumor entities, partially synergistic effects were revealed when BOLD-100 was combined with the drugs mentioned above. The DCFH-DA assay suggested consistent increases of ROS levels after treatment with oxaliplatin and, with restrictions, its combination with BOLD-100. Apoptosis and necrosis were induced in the spheroid models by single-drug and combined treatment, with no hints at antagonism in the combination settings. In conclusion, these findings emphasize the potential of BOLD-100 for combination therapy of gastric and colorectal cancers.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Spheroids, Cellular/drug effects
*Antineoplastic Combined Chemotherapy Protocols/pharmacology/administration & dosage
Apoptosis/drug effects
Reactive Oxygen Species/metabolism
Drug Synergism
Oxaliplatin
Endoplasmic Reticulum Chaperone BiP
Cell Line, Tumor
HT29 Cells
Fluorouracil/administration & dosage/pharmacology
Cisplatin/administration & dosage/pharmacology
HCT116 Cells
Organoplatinum Compounds/administration & dosage/pharmacology
Irinotecan
*Gastrointestinal Neoplasms/drug therapy/pathology
*Organometallic Compounds/pharmacology/administration & dosage
*Stomach Neoplasms/drug therapy/pathology
Antineoplastic Agents/pharmacology
RevDate: 2026-05-22
Evidence for an Early Cadherin-Catenin Interaction Network in Ctenophores.
Molecular biology and evolution pii:8691028 [Epub ahead of print].
The Cadherin-Catenin Complex (CCC) is a calcium-dependent assembly that is essential for the organization and function of animal cells and tissues. CCC components form adherens junctions that link cell adhesion to the actin cytoskeleton and important signaling pathways that control processes like gene expression, cell polarity, and growth. While the CCC has been extensively studied and known to be conserved across most metazoan lineages, its occurrence in ctenophores, one of the earliest branching groups, has been questioned, with implications for the origins of multicellularity in animals. Here, we show that the ctenophore Mnemiopsis leidyi possesses a reduced cadherin repertoire yet retains conserved interactions characteristic of the CCC. Phylogenetic analyses identified a novel ctenophore-specific cadherin phylogenetically distant from major cadherin families from other animals. Screening a custom yeast 2-hybrid library, derived from M. leidyi embryo cDNA, with the cytoplasmic tail of this non-canonical cadherin-like protein identified known CCC components β-catenin, p120, and Hakai as interacting proteins. Similarly, a screen using M. leidyi α-catenin as bait identified β-catenin, vinculin, and other known actin cytoskeleton-associated proteins. Directed yeast 2-hybrid assays confirmed key interactions and demonstrated that targeted mutagenesis of conserved residues abolished binding, as is observed in other metazoans. Together, these findings suggest that core molecular interactions underlying the CCC are conserved in M. leidyi, consistent with the hypothesis that a functional CCC was an ancestral trait foundational to the evolution of multicellular animals.
Additional Links: PMID-42172677
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42172677,
year = {2026},
author = {Guttieres, LJ and Singh, A and Senatore, A and Martindale, MQ},
title = {Evidence for an Early Cadherin-Catenin Interaction Network in Ctenophores.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msag123},
pmid = {42172677},
issn = {1537-1719},
abstract = {The Cadherin-Catenin Complex (CCC) is a calcium-dependent assembly that is essential for the organization and function of animal cells and tissues. CCC components form adherens junctions that link cell adhesion to the actin cytoskeleton and important signaling pathways that control processes like gene expression, cell polarity, and growth. While the CCC has been extensively studied and known to be conserved across most metazoan lineages, its occurrence in ctenophores, one of the earliest branching groups, has been questioned, with implications for the origins of multicellularity in animals. Here, we show that the ctenophore Mnemiopsis leidyi possesses a reduced cadherin repertoire yet retains conserved interactions characteristic of the CCC. Phylogenetic analyses identified a novel ctenophore-specific cadherin phylogenetically distant from major cadherin families from other animals. Screening a custom yeast 2-hybrid library, derived from M. leidyi embryo cDNA, with the cytoplasmic tail of this non-canonical cadherin-like protein identified known CCC components β-catenin, p120, and Hakai as interacting proteins. Similarly, a screen using M. leidyi α-catenin as bait identified β-catenin, vinculin, and other known actin cytoskeleton-associated proteins. Directed yeast 2-hybrid assays confirmed key interactions and demonstrated that targeted mutagenesis of conserved residues abolished binding, as is observed in other metazoans. Together, these findings suggest that core molecular interactions underlying the CCC are conserved in M. leidyi, consistent with the hypothesis that a functional CCC was an ancestral trait foundational to the evolution of multicellular animals.},
}
RevDate: 2026-05-21
CmpDate: 2026-05-21
The evolution of gene functional repertoire in Amorphea: divergent strategies across Amoebozoa, Fungi, and Metazoa.
Molecular biology and evolution, 43(5):.
Metazoa and Fungi have been extensively studied to reconstruct the trajectory of Opisthokont evolution. Their sister group, Amoebozoa, provides additional potential to generate valuable insights into the origins of Opisthokont lineages. Amoebozoa represent a diverse group of amoeboid organisms, which have adapted to a wide range of environments and ecological niches. Studying Amoebozoa not only helps to illuminate Opisthokont evolution but also reveals the mechanisms that have driven amoebozoan ecological success. Here, we report the discovery of Apostamoeba explorator strain BEAP0066, representing a novel lineage within Amoebozoa with intriguing behaviors like the "double-amoeba," a behavior characterized by the bipolarization of a cell into two poles that coexist and act as two semi-independent cells. By analyzing the gene content of A. explorator and diverse amoebozoans with ancestral gene content reconstructions, correspondence analyses of Clusters of Orthologous Groups category composition and protein families database (Pfam) clan clustering, we revealed distinct evolutionary trajectories for Amoebozoa, Metazoa, and Fungi. Amoebozoa retained an ancestral Amorphea-like state, characterized by an enrichment of genes related to motility, phagocytosis, and rapid cellular response, while Metazoa specialized in multicellularity-related genes and Fungi in metabolism and transport. These findings suggest that retention of gene function composition, rather than gene loss, played a key role in shaping Amoebozoa evolution.
Additional Links: PMID-42165094
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42165094,
year = {2026},
author = {Gàlvez-Morante, A and Berney, C and Richter, DJ},
title = {The evolution of gene functional repertoire in Amorphea: divergent strategies across Amoebozoa, Fungi, and Metazoa.},
journal = {Molecular biology and evolution},
volume = {43},
number = {5},
pages = {},
doi = {10.1093/molbev/msag071},
pmid = {42165094},
issn = {1537-1719},
support = {/ERC_/European Research Council/International ; 949745//European Union's Horizon 2020 research and innovation/ ; 101097659//European Union's Horizon 2020 research and innovation/ ; QC2021-007134-P//Departament de Recerca i Universitats de la Generalitat de Catalunya/ ; MICIU/AEI/10.13039/501100011033//Departament de Recerca i Universitats de la Generalitat de Catalunya/ ; //ERDF/EU/ ; },
mesh = {*Amoebozoa/genetics ; *Evolution, Molecular ; Phylogeny ; *Fungi/genetics ; Animals ; Biological Evolution ; },
abstract = {Metazoa and Fungi have been extensively studied to reconstruct the trajectory of Opisthokont evolution. Their sister group, Amoebozoa, provides additional potential to generate valuable insights into the origins of Opisthokont lineages. Amoebozoa represent a diverse group of amoeboid organisms, which have adapted to a wide range of environments and ecological niches. Studying Amoebozoa not only helps to illuminate Opisthokont evolution but also reveals the mechanisms that have driven amoebozoan ecological success. Here, we report the discovery of Apostamoeba explorator strain BEAP0066, representing a novel lineage within Amoebozoa with intriguing behaviors like the "double-amoeba," a behavior characterized by the bipolarization of a cell into two poles that coexist and act as two semi-independent cells. By analyzing the gene content of A. explorator and diverse amoebozoans with ancestral gene content reconstructions, correspondence analyses of Clusters of Orthologous Groups category composition and protein families database (Pfam) clan clustering, we revealed distinct evolutionary trajectories for Amoebozoa, Metazoa, and Fungi. Amoebozoa retained an ancestral Amorphea-like state, characterized by an enrichment of genes related to motility, phagocytosis, and rapid cellular response, while Metazoa specialized in multicellularity-related genes and Fungi in metabolism and transport. These findings suggest that retention of gene function composition, rather than gene loss, played a key role in shaping Amoebozoa evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Amoebozoa/genetics
*Evolution, Molecular
Phylogeny
*Fungi/genetics
Animals
Biological Evolution
RevDate: 2026-05-20
CmpDate: 2026-05-20
SWI3A/B regulates the transition from vegetative to reproductive phase in the liverwort Marchantia polymorpha.
Plant reproduction, 39(2):.
Land plants alternate between multicellular haploid and diploid phases, requiring a tight coordination between vegetative growth and sexual reproduction. We investigated SWI3A/B, an ancient core subunit of the SWI/SNF complex, of the non-vascular liverwort Marchantia polymorpha. A mutation in the promoter of MpSWI3A/B affected gametangiophore development and spermiogenesis in males, revealing its male-specific role in reproductive development. The MpSWIA/B mutant line amplifies vegetative propagation in males under conditions that would normally induce reproductive growth. The phenotype was underpinned by transcriptomic changes, showing that MpSWI3A/B modulates key regulators of gametangiophore initiation (e.g. BONOBO, GLID), sperm development and motility (e.g. DUO1, PKAR), and asexual reproduction (e.g. KAI2). We propose that, as a chromatin-level regulator, MpSWI3A/B may contribute to balancing vegetative and reproductive phases and highlight the protein's potential when exploring ancient epigenetic functions that coordinate developmental phase transitions in land plants.
Additional Links: PMID-42159614
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42159614,
year = {2026},
author = {Lozano-Quiles, M and Raval, PK and Rensing, SA and Gould, SB},
title = {SWI3A/B regulates the transition from vegetative to reproductive phase in the liverwort Marchantia polymorpha.},
journal = {Plant reproduction},
volume = {39},
number = {2},
pages = {},
pmid = {42159614},
issn = {2194-7961},
mesh = {*Marchantia/genetics/growth & development/physiology ; *Plant Proteins/genetics/metabolism ; Reproduction/genetics ; Gene Expression Regulation, Plant ; Mutation ; },
abstract = {Land plants alternate between multicellular haploid and diploid phases, requiring a tight coordination between vegetative growth and sexual reproduction. We investigated SWI3A/B, an ancient core subunit of the SWI/SNF complex, of the non-vascular liverwort Marchantia polymorpha. A mutation in the promoter of MpSWI3A/B affected gametangiophore development and spermiogenesis in males, revealing its male-specific role in reproductive development. The MpSWIA/B mutant line amplifies vegetative propagation in males under conditions that would normally induce reproductive growth. The phenotype was underpinned by transcriptomic changes, showing that MpSWI3A/B modulates key regulators of gametangiophore initiation (e.g. BONOBO, GLID), sperm development and motility (e.g. DUO1, PKAR), and asexual reproduction (e.g. KAI2). We propose that, as a chromatin-level regulator, MpSWI3A/B may contribute to balancing vegetative and reproductive phases and highlight the protein's potential when exploring ancient epigenetic functions that coordinate developmental phase transitions in land plants.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Marchantia/genetics/growth & development/physiology
*Plant Proteins/genetics/metabolism
Reproduction/genetics
Gene Expression Regulation, Plant
Mutation
RevDate: 2026-05-19
Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15[+] Fibroblast Formation During Pancreatic Ductal Adenocarcinoma Development.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive and desmoplastic tumor microenvironment (TME) that limits the efficacy of immunotherapy. However, the evolution of this immunosuppressive TME and the underlying mechanisms remain incompletely understood. Here, we construct a dynamic single-cell atlas spanning uninvolved adjacent pancreatic tissue (UNIN), intraductal papillary mucinous neoplasm (IPMN), and PDAC. We confirm the stepwise establishment of an immunosuppressive milieu, accompanied by the emergence of LRRC15[+] fibroblasts as determinants. Functional assays further identify tumor-derived LAMB3 as a regulator of LRRC15[+] fibroblast differentiation. Mechanistically, LAMB3 promotes FOSL2-dependent transcriptional activation of LRRC15 through the ITGB1/FAK/MAPK signaling axis, ultimately suppressing T cell cytotoxicity. Orthotopic models reveal that LAMB3 overexpression increases the LRRC15 positive area and impairs T cell cytotoxicity, whereas FAK inhibition partially reverses these effects. In parallel, LAMB3 knockdown reduces the LRRC15 positive area and improves the efficacy of PD-1 blockade. Moreover, glycolytic reprogramming in PDAC ductal cells upregulates LAMB3 expression and correlates with increased LRRC15[+] fibroblast enrichment. Clinically, co-enrichment of LAMB3[+] PDAC ductal cells and LRRC15[+] fibroblasts is associated with inferior overall survival. Collectively, our findings define a dynamic ductal-fibroblast-immune multicellular axis underlying PDAC pathogenesis and provide insights into potential therapeutic strategies.
Additional Links: PMID-42154006
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42154006,
year = {2026},
author = {Shi, X and Liu, H and Sun, J and Liu, X and Jv, X and Chen, L and Zhang, Y and Zhang, H and Xing, X and Li, R and Ke, X and Wang, J and Yin, X and Liu, B and Liu, Q and Wang, Y and Lu, J and Liu, S and Pang, J and Cai, Y and Dai, M and Bai, F and Wu, H and Liang, Z},
title = {Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15[+] Fibroblast Formation During Pancreatic Ductal Adenocarcinoma Development.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e20029},
doi = {10.1002/advs.202520029},
pmid = {42154006},
issn = {2198-3844},
support = {2024-2-4012//Capital's Funds for Health Improvement and Research (CFH)/ ; 2025-PUMCH-D-002//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-B-061//National High Level Hospital Clinical Research Funding/ ; 2025YFC3410200//National Key Research and Development Program of China/ ; T2125002//National Science Fund for Distinguished Young Scholars/ ; 2025ZD0544800//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 2023-I2M-C&T-B-022//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; L252174//Beijing Municipal Natural Science Foundation/ ; 82403474//National Natural Science Foundation of China/ ; },
abstract = {Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive and desmoplastic tumor microenvironment (TME) that limits the efficacy of immunotherapy. However, the evolution of this immunosuppressive TME and the underlying mechanisms remain incompletely understood. Here, we construct a dynamic single-cell atlas spanning uninvolved adjacent pancreatic tissue (UNIN), intraductal papillary mucinous neoplasm (IPMN), and PDAC. We confirm the stepwise establishment of an immunosuppressive milieu, accompanied by the emergence of LRRC15[+] fibroblasts as determinants. Functional assays further identify tumor-derived LAMB3 as a regulator of LRRC15[+] fibroblast differentiation. Mechanistically, LAMB3 promotes FOSL2-dependent transcriptional activation of LRRC15 through the ITGB1/FAK/MAPK signaling axis, ultimately suppressing T cell cytotoxicity. Orthotopic models reveal that LAMB3 overexpression increases the LRRC15 positive area and impairs T cell cytotoxicity, whereas FAK inhibition partially reverses these effects. In parallel, LAMB3 knockdown reduces the LRRC15 positive area and improves the efficacy of PD-1 blockade. Moreover, glycolytic reprogramming in PDAC ductal cells upregulates LAMB3 expression and correlates with increased LRRC15[+] fibroblast enrichment. Clinically, co-enrichment of LAMB3[+] PDAC ductal cells and LRRC15[+] fibroblasts is associated with inferior overall survival. Collectively, our findings define a dynamic ductal-fibroblast-immune multicellular axis underlying PDAC pathogenesis and provide insights into potential therapeutic strategies.},
}
RevDate: 2026-05-19
CmpDate: 2026-05-19
Lineage priming and cell type proportioning depends on the interplay between stochastic and deterministic factors.
eLife, 14: pii:105512.
Isogenic cells can break symmetry and adopt different fates, even when exposed to a seemingly identical environment. This deeply conserved phenomenon allows unicellular organisms to pre-empt dynamically changing environments and is central to the evolution of multicellularity. It is thought that cells are primed towards different lineages by cell-cell variation, although the underlying mechanisms are poorly understood. To address this, we exploit the tractability of the social amoeba Dictyostelium discoideum, where cell fate choice also does not depend on spatial cues. We develop and test a model to explain quantitative experimental single-cell observations of probabilistic differentiation. The model suggests that cell cycle position affects lineage choice, as previously shown but that stochastic cell-cell variation also plays a key role. Single cell sequencing reveals genes that exhibit cell type-specific expression or genes that affect fate choice exhibit extensive stochastic cell-cell expression variation. Like lineage priming genes in ESCs, they are associated with H3K4 methylation, which when perturbed affects their expression and disrupt fate choice. We suggest the integration of stochastic and deterministic inputs represents an adaptive mechanism to increase developmental robustness against perturbations that affect deterministic signals.
Additional Links: PMID-42154822
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42154822,
year = {2026},
author = {Salvidge, W and Brimson, C and Gruenheit, N and Huang, LY and Pears, C and Wolf, J and Thompson, C},
title = {Lineage priming and cell type proportioning depends on the interplay between stochastic and deterministic factors.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
doi = {10.7554/eLife.105512},
pmid = {42154822},
issn = {2050-084X},
support = {10.35802/095643//Wellcome/ ; NE/V012002/1//Natural Environment Research Council/ ; },
mesh = {*Dictyostelium/genetics/cytology/physiology ; *Cell Lineage ; Stochastic Processes ; *Cell Differentiation ; Single-Cell Analysis ; Models, Biological ; Cell Cycle ; },
abstract = {Isogenic cells can break symmetry and adopt different fates, even when exposed to a seemingly identical environment. This deeply conserved phenomenon allows unicellular organisms to pre-empt dynamically changing environments and is central to the evolution of multicellularity. It is thought that cells are primed towards different lineages by cell-cell variation, although the underlying mechanisms are poorly understood. To address this, we exploit the tractability of the social amoeba Dictyostelium discoideum, where cell fate choice also does not depend on spatial cues. We develop and test a model to explain quantitative experimental single-cell observations of probabilistic differentiation. The model suggests that cell cycle position affects lineage choice, as previously shown but that stochastic cell-cell variation also plays a key role. Single cell sequencing reveals genes that exhibit cell type-specific expression or genes that affect fate choice exhibit extensive stochastic cell-cell expression variation. Like lineage priming genes in ESCs, they are associated with H3K4 methylation, which when perturbed affects their expression and disrupt fate choice. We suggest the integration of stochastic and deterministic inputs represents an adaptive mechanism to increase developmental robustness against perturbations that affect deterministic signals.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Dictyostelium/genetics/cytology/physiology
*Cell Lineage
Stochastic Processes
*Cell Differentiation
Single-Cell Analysis
Models, Biological
Cell Cycle
RevDate: 2026-05-18
CmpDate: 2026-05-18
Multinucleation as a recurring evolutionary strategy for scaling and plasticity.
Current biology : CB, 36(10):R450-R463.
Multinucleate cells - single cells containing multiple nuclei in a shared cytoplasm - are found across the eukaryotic tree of life. Having evolved independently in fungi, plants, protists, and animals, they thrive in environments ranging from nutrient-poor deep-sea sediments to dynamic soil microhabitats and host tissues. Multinucleate organization enables spatial specialization without internal partitions and facilitates rapid scaling of metabolic or transcriptional capacity, allowing organisms to forage across patchy resources, withstand physical stress, and respond quickly to environmental fluctuations. Yet multinucleation also brings challenges, including diffusion limits, the need for nuclear coordination, and the potential for genetic conflict. Its repeated emergence, often in lineages that have also evolved multicellularity, points to shared cellular, structural, and regulatory prerequisites shaped by ecological pressures. Here, we integrate perspectives from cell biology, ecology, and evolution to demonstrate that multinucleation is not a rare anomaly but a fundamental organizational strategy. Recognizing these systems as adaptive responses to environmental constraints provides a framework for uncovering general principles of cellular organization, evolution of life-cycle strategies, and the diversification of complex life.
Additional Links: PMID-42150533
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42150533,
year = {2026},
author = {Dey, G and Ganter, M and Jacobovitz, M},
title = {Multinucleation as a recurring evolutionary strategy for scaling and plasticity.},
journal = {Current biology : CB},
volume = {36},
number = {10},
pages = {R450-R463},
doi = {10.1016/j.cub.2026.03.066},
pmid = {42150533},
issn = {1879-0445},
mesh = {*Biological Evolution ; Animals ; *Cell Nucleus/physiology ; },
abstract = {Multinucleate cells - single cells containing multiple nuclei in a shared cytoplasm - are found across the eukaryotic tree of life. Having evolved independently in fungi, plants, protists, and animals, they thrive in environments ranging from nutrient-poor deep-sea sediments to dynamic soil microhabitats and host tissues. Multinucleate organization enables spatial specialization without internal partitions and facilitates rapid scaling of metabolic or transcriptional capacity, allowing organisms to forage across patchy resources, withstand physical stress, and respond quickly to environmental fluctuations. Yet multinucleation also brings challenges, including diffusion limits, the need for nuclear coordination, and the potential for genetic conflict. Its repeated emergence, often in lineages that have also evolved multicellularity, points to shared cellular, structural, and regulatory prerequisites shaped by ecological pressures. Here, we integrate perspectives from cell biology, ecology, and evolution to demonstrate that multinucleation is not a rare anomaly but a fundamental organizational strategy. Recognizing these systems as adaptive responses to environmental constraints provides a framework for uncovering general principles of cellular organization, evolution of life-cycle strategies, and the diversification of complex life.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Biological Evolution
Animals
*Cell Nucleus/physiology
RevDate: 2026-05-16
Rethinking the origins and functions of adaptive immunity.
Trends in immunology pii:S1471-4906(26)00101-8 [Epub ahead of print].
The adaptive immune system (AIS) is traditionally viewed as a defensive vertebrate innovation forged by pathogen pressure. Yet many of its core features suggest it is a homeostatic, regulatory circuit, not simply a sophisticated means of antimicrobial warfare. The horizontal transfer of mitochondria--endogenous endosymbiotic organelles-is a conserved mechanism for maintaining tissue homeostasis through metabolic rescue but can alter a cell's identity and provoke immune responses. We propose that escalating multicellular complexity accommodated mitochondrial mobility-and the inevitable intrinsic immunological danger it presents-through a complementary supervisory system with buffering (tolerance), contextualization (specificity), memory, and eliminatory capacities. This perspective reframes the AIS as a constitutive danger management network, integrating tissue homeostasis, metabolic surveillance, immune tolerance, and immunological defense.
Additional Links: PMID-42142972
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42142972,
year = {2026},
author = {Okwan-Duodu, D and Sperling, EA and Engleman, EG},
title = {Rethinking the origins and functions of adaptive immunity.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2026.04.008},
pmid = {42142972},
issn = {1471-4981},
abstract = {The adaptive immune system (AIS) is traditionally viewed as a defensive vertebrate innovation forged by pathogen pressure. Yet many of its core features suggest it is a homeostatic, regulatory circuit, not simply a sophisticated means of antimicrobial warfare. The horizontal transfer of mitochondria--endogenous endosymbiotic organelles-is a conserved mechanism for maintaining tissue homeostasis through metabolic rescue but can alter a cell's identity and provoke immune responses. We propose that escalating multicellular complexity accommodated mitochondrial mobility-and the inevitable intrinsic immunological danger it presents-through a complementary supervisory system with buffering (tolerance), contextualization (specificity), memory, and eliminatory capacities. This perspective reframes the AIS as a constitutive danger management network, integrating tissue homeostasis, metabolic surveillance, immune tolerance, and immunological defense.},
}
RevDate: 2026-05-15
CmpDate: 2026-05-15
A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.
Frontiers in immunology, 17:1823101.
Human atherosclerosis is increasingly recognized as a spatially organized inflammatory disease in which macrophages act as central regulators of lesion evolution rather than as a uniform foam-cell population. Recent single-cell and spatial profiling studies have redefined plaque macrophages as reproducible state programs, including inflammatory, interferon-responsive, lipid-associated, foamy, resident-like, and reparative phenotypes, each embedded within distinct microanatomic niches and multicellular communication networks. These programs are not merely descriptive, but are linked to clinically relevant features such as symptomatic disease, necrotic core expansion, fibrous cap thinning, extracellular matrix remodeling, and recurrent vascular risk. At the same time, the field remains limited by heterogeneity in plaque procurement, anatomic annotation, computational integration, and state nomenclature, which complicates cross-study comparison and obscures biological concordance. This review summarizes the recent advances in human plaque single-cell, spatial transcriptomic, and integrative multi-omics studies to outline the emerging architecture of macrophage states in atherosclerosis. We examine how atlas-scale frameworks connect state definition with spatial localization, regulatory circuitry, and lesion behavior, and discuss how these insights refine mechanistic understanding of plaque progression. We further highlight the translational potential of macrophage-state signatures for risk stratification, molecular imaging, and therapeutic targeting. A coherent human plaque macrophage atlas offers a conceptual and practical framework for moving from descriptive heterogeneity toward clinically actionable biology in atherosclerotic disease.
Additional Links: PMID-42136660
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42136660,
year = {2026},
author = {Yang, Y and Zhu, H},
title = {A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1823101},
pmid = {42136660},
issn = {1664-3224},
mesh = {Humans ; *Plaque, Atherosclerotic/pathology/immunology/metabolism ; *Atherosclerosis/pathology/immunology/metabolism/etiology ; *Macrophages/immunology/pathology/metabolism ; Single-Cell Analysis ; Transcriptome ; },
abstract = {Human atherosclerosis is increasingly recognized as a spatially organized inflammatory disease in which macrophages act as central regulators of lesion evolution rather than as a uniform foam-cell population. Recent single-cell and spatial profiling studies have redefined plaque macrophages as reproducible state programs, including inflammatory, interferon-responsive, lipid-associated, foamy, resident-like, and reparative phenotypes, each embedded within distinct microanatomic niches and multicellular communication networks. These programs are not merely descriptive, but are linked to clinically relevant features such as symptomatic disease, necrotic core expansion, fibrous cap thinning, extracellular matrix remodeling, and recurrent vascular risk. At the same time, the field remains limited by heterogeneity in plaque procurement, anatomic annotation, computational integration, and state nomenclature, which complicates cross-study comparison and obscures biological concordance. This review summarizes the recent advances in human plaque single-cell, spatial transcriptomic, and integrative multi-omics studies to outline the emerging architecture of macrophage states in atherosclerosis. We examine how atlas-scale frameworks connect state definition with spatial localization, regulatory circuitry, and lesion behavior, and discuss how these insights refine mechanistic understanding of plaque progression. We further highlight the translational potential of macrophage-state signatures for risk stratification, molecular imaging, and therapeutic targeting. A coherent human plaque macrophage atlas offers a conceptual and practical framework for moving from descriptive heterogeneity toward clinically actionable biology in atherosclerotic disease.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Plaque, Atherosclerotic/pathology/immunology/metabolism
*Atherosclerosis/pathology/immunology/metabolism/etiology
*Macrophages/immunology/pathology/metabolism
Single-Cell Analysis
Transcriptome
RevDate: 2026-05-15
CmpDate: 2026-05-15
Cancer, collapse, and the politics of somatic evolution.
Evolution, medicine, and public health, 14(1):1-10.
Multicellularity rests on a social contract: cells give up autonomy in exchange for shared resources, division of labour, and protection. Cancer is what happens when that contract collapses, and somatic evolution runs loose inside the body. Here, the multicellular social contract is used as a framework to recast tumour suppressors, tissue architecture, and immune surveillance as enforcement devices, and cancer as a 'rogue society' where cheater lineages exploit public goods, remodel niches, and build hierarchies. This perspective links clonal evolution, phenotypic plasticity, and therapy resistance to the 'politics' of rules and enforcement, and points towards therapies that do not just kill malignant cells but actively reshape the conditions under which somatic evolution proceeds.
Additional Links: PMID-42136800
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42136800,
year = {2026},
author = {Salzet, M},
title = {Cancer, collapse, and the politics of somatic evolution.},
journal = {Evolution, medicine, and public health},
volume = {14},
number = {1},
pages = {1-10},
pmid = {42136800},
issn = {2050-6201},
abstract = {Multicellularity rests on a social contract: cells give up autonomy in exchange for shared resources, division of labour, and protection. Cancer is what happens when that contract collapses, and somatic evolution runs loose inside the body. Here, the multicellular social contract is used as a framework to recast tumour suppressors, tissue architecture, and immune surveillance as enforcement devices, and cancer as a 'rogue society' where cheater lineages exploit public goods, remodel niches, and build hierarchies. This perspective links clonal evolution, phenotypic plasticity, and therapy resistance to the 'politics' of rules and enforcement, and points towards therapies that do not just kill malignant cells but actively reshape the conditions under which somatic evolution proceeds.},
}
RevDate: 2026-05-15
Evolution of Gills Across the Animal Kingdom.
Integrative and comparative biology pii:8678853 [Epub ahead of print].
Gills are a feature of many aquatic animals, serving to extract oxygen from the water and to maintain ionic balance between the bloodstream and the environment. While gills first arose in early multicellular animals, their great diversity of forms make it unclear the extent to which they represent a continuously evolving structure or an example of convergent evolution. In chordates including vertebrates, gill filaments develop as outgrowths of epithelia, which also generate the gill slits and pores. The mesenchymal component derives from cranial neural crest cell progenitors in vertebrates and generates skeletal and connective tissues that support the gills and underlying vasculature. In this perspective, we discuss the evolutionary origins of gills in bilateria, the extent to which they are related to tentacles and other filamentous appendages, and how the repurposing of gill programs may have generated novel structures during the water to land transition, such as the book lungs of spiders and the outer ear and epiglottis of mammals. The gill filaments and gill-like tentacles of diverse marine invertebrates also frequently share a distinct type of cellular cartilage reminiscent of the elastic cartilage in vertebrate gill filaments and outer ears, suggesting that cartilage may have first arisen in gill-like structures of early bilateria. Elastic cartilage of vertebrates may therefore represent a vestige of invertebrate cartilage that pre-dates the vertebrate-specific hyaline cartilage of endochondral bones. We also discuss the possibility that the Dlx-expressing pharyngeal arches of vertebrates reflect elaborations of invertebrate gill and tentacle appendages that expressed the Dlx homolog distalless, with the gill filament elastic cartilage and gill-support endochondral bones deriving from distinct domains of the same Dlx-positive arches. These studies point to ancestral gills as a potentially rich source of morphological innovations across deep evolutionary time.
Additional Links: PMID-42138641
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42138641,
year = {2026},
author = {Thiruppathy, M and Crump, JG},
title = {Evolution of Gills Across the Animal Kingdom.},
journal = {Integrative and comparative biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/icb/icag046},
pmid = {42138641},
issn = {1557-7023},
abstract = {Gills are a feature of many aquatic animals, serving to extract oxygen from the water and to maintain ionic balance between the bloodstream and the environment. While gills first arose in early multicellular animals, their great diversity of forms make it unclear the extent to which they represent a continuously evolving structure or an example of convergent evolution. In chordates including vertebrates, gill filaments develop as outgrowths of epithelia, which also generate the gill slits and pores. The mesenchymal component derives from cranial neural crest cell progenitors in vertebrates and generates skeletal and connective tissues that support the gills and underlying vasculature. In this perspective, we discuss the evolutionary origins of gills in bilateria, the extent to which they are related to tentacles and other filamentous appendages, and how the repurposing of gill programs may have generated novel structures during the water to land transition, such as the book lungs of spiders and the outer ear and epiglottis of mammals. The gill filaments and gill-like tentacles of diverse marine invertebrates also frequently share a distinct type of cellular cartilage reminiscent of the elastic cartilage in vertebrate gill filaments and outer ears, suggesting that cartilage may have first arisen in gill-like structures of early bilateria. Elastic cartilage of vertebrates may therefore represent a vestige of invertebrate cartilage that pre-dates the vertebrate-specific hyaline cartilage of endochondral bones. We also discuss the possibility that the Dlx-expressing pharyngeal arches of vertebrates reflect elaborations of invertebrate gill and tentacle appendages that expressed the Dlx homolog distalless, with the gill filament elastic cartilage and gill-support endochondral bones deriving from distinct domains of the same Dlx-positive arches. These studies point to ancestral gills as a potentially rich source of morphological innovations across deep evolutionary time.},
}
RevDate: 2026-05-13
Genipin-Crosslinked, Silane-Anchored 3D Tumor-Stroma Microtissues for High-Content On-Chip Drug Testing.
Advanced healthcare materials [Epub ahead of print].
Physiologically relevant 3D tumor models incorporating extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) are essential for studying tumor progression and drug resistance, yet often suffer from hydrogel contraction and instability-especially in microfluidic formats, where ECM deformation hampers long-term culture and quantitative imaging. Here, we present a microfluidic tumor-fibroblast co-culture platform for head and neck squamous cell carcinoma (HNSCC) that overcomes these limitations via a dual strategy: APTES-mediated surface silanization anchors the ECM to the chip, combined with Genipin-based crosslinking, which modestly increases hydrogel stiffness and progressively reinforces the network without compromising cell viability, as confirmed by time- and frequency-resolved rheology. Fourier-transform infrared spectroscopy (FTIR) verified successful collagen crosslinking while preserving reactive ─OH and ─NH2 groups, enabling covalent bonding to the APTES-functionalized chip. The platform further integrates semi-automated segmentation and high-content imaging to quantify dynamic phenotypic drug responses at both single-cell and multicellular/tissue organization levels. Drug chemosensitivity assays, including co-culture with patient-derived CAFs, enabled quantitative assessment of clinically relevant chemoprotective effects. By combining biomaterial engineering with functional microfluidic design, this system enables reproducible, physiologically relevant modeling of tumor-fibroblast interactions, offering a scalable tool for preclinical drug chemosensitivity screening and clinical translation.
Additional Links: PMID-42121382
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42121382,
year = {2026},
author = {Le Manach, D and Kowsari-Esfahan, R and Reszczyńska, E and Nghe, P and Nees, M},
title = {Genipin-Crosslinked, Silane-Anchored 3D Tumor-Stroma Microtissues for High-Content On-Chip Drug Testing.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e03566},
doi = {10.1002/adhm.202503566},
pmid = {42121382},
issn = {2192-2659},
support = {UMO-2020/37/B/NZ4/03920//National Science Centre (NCN)/ ; DEC-2021/41/B/NZ7/03786//National Science Centre (NCN)/ ; 10698//EMBO Scientific Exchange/ ; 309372//Academy of Finland "Phenotypic Screening for Cancer Drug Discovery"/Consortium: PESCADoR/ ; ANR-10-EQPX-34//Institut Pierre-Gilles de Gennes/ ; Grant ERC PoC (101100823)//EU Horizon 2020/ ; PPI/APM/2019/1/00089/U/00001//Narodowa Agencja Wymiany Akademickiej/ ; //PSL QLife initiative/ ; },
abstract = {Physiologically relevant 3D tumor models incorporating extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) are essential for studying tumor progression and drug resistance, yet often suffer from hydrogel contraction and instability-especially in microfluidic formats, where ECM deformation hampers long-term culture and quantitative imaging. Here, we present a microfluidic tumor-fibroblast co-culture platform for head and neck squamous cell carcinoma (HNSCC) that overcomes these limitations via a dual strategy: APTES-mediated surface silanization anchors the ECM to the chip, combined with Genipin-based crosslinking, which modestly increases hydrogel stiffness and progressively reinforces the network without compromising cell viability, as confirmed by time- and frequency-resolved rheology. Fourier-transform infrared spectroscopy (FTIR) verified successful collagen crosslinking while preserving reactive ─OH and ─NH2 groups, enabling covalent bonding to the APTES-functionalized chip. The platform further integrates semi-automated segmentation and high-content imaging to quantify dynamic phenotypic drug responses at both single-cell and multicellular/tissue organization levels. Drug chemosensitivity assays, including co-culture with patient-derived CAFs, enabled quantitative assessment of clinically relevant chemoprotective effects. By combining biomaterial engineering with functional microfluidic design, this system enables reproducible, physiologically relevant modeling of tumor-fibroblast interactions, offering a scalable tool for preclinical drug chemosensitivity screening and clinical translation.},
}
RevDate: 2026-05-13
The Double-Edged Nature of β-Catenin: From Multicellular Innovation to Cancer Vulnerability.
American journal of physiology. Cell physiology [Epub ahead of print].
β-catenin embodies a fundamental paradox of multicellular life. The same molecular system that enabled the emergence of animal multicellularity by coupling cell-cell adhesion to gene regulation also creates a vulnerability that can drive cancer when misregulated. As a central regulator of cell physiology, β-catenin integrates cell-cell adhesion, mechanotransduction, and gene expression to coordinate tissue architecture with transcriptional programs controlling proliferation, differentiation, and homeostasis. Phylogenomic analyses indicate that bona fide β-catenins form a metazoan-specific monophyletic clade derived from an ancestral armadillo-repeat scaffold. This conserved superhelical structure generates a single interaction groove that mediates mutually exclusive binding to E-cadherin, adenomatous polyposis coli (APC), and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. While this architecture enabled early metazoans to coordinate adhesion, signaling, and morphogenesis, it also introduced an intrinsic regulatory vulnerability. Mutations that disrupt β-catenin degradation stabilize the protein, uncoupling Wnt signaling from its normal regulatory constraints and driving persistent proliferative transcriptional programs. In parallel, emerging structural and biophysical studies reveal conformational plasticity and mechanosensitive properties that enable dynamic partitioning between adhesive and signaling pools. Disruption of these regulatory layers promotes tumor progression, metastasis, immune evasion, and therapy resistance, positioning β-catenin as both a central oncogenic node and a challenging therapeutic target. In this review, we integrate evolutionary, structural, and mechanobiological perspectives to illustrate how β-catenin exemplifies the double-edged nature of biological innovation, an ancient protein that enabled multicellular organization yet whose dysregulation underlies fundamental mechanisms of human cancer.
Additional Links: PMID-42126086
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42126086,
year = {2026},
author = {Garrido-Faúndez, V and Castro, B and Weil Echeverría, C and Sandoval Baeza, F and Sánchez González, VP and Robinson, F and Ravasio, A and Owen, GI and Bertocchi, C},
title = {The Double-Edged Nature of β-Catenin: From Multicellular Innovation to Cancer Vulnerability.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00175.2026},
pmid = {42126086},
issn = {1522-1563},
support = {1250073//ANID | Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT)/ ; 1220586//ANID | Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT)/ ; Nucleo Milenio NCN2024_068//Agencia Nacional de Investigación y Desarrollo (ANID)/ ; 152220002//ANID | Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP)/ ; 15130011//ANID | Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP)/ ; APOYO 1523A0008//Agencia Nacional de Investigación y Desarrollo (ANID)/ ; },
abstract = {β-catenin embodies a fundamental paradox of multicellular life. The same molecular system that enabled the emergence of animal multicellularity by coupling cell-cell adhesion to gene regulation also creates a vulnerability that can drive cancer when misregulated. As a central regulator of cell physiology, β-catenin integrates cell-cell adhesion, mechanotransduction, and gene expression to coordinate tissue architecture with transcriptional programs controlling proliferation, differentiation, and homeostasis. Phylogenomic analyses indicate that bona fide β-catenins form a metazoan-specific monophyletic clade derived from an ancestral armadillo-repeat scaffold. This conserved superhelical structure generates a single interaction groove that mediates mutually exclusive binding to E-cadherin, adenomatous polyposis coli (APC), and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. While this architecture enabled early metazoans to coordinate adhesion, signaling, and morphogenesis, it also introduced an intrinsic regulatory vulnerability. Mutations that disrupt β-catenin degradation stabilize the protein, uncoupling Wnt signaling from its normal regulatory constraints and driving persistent proliferative transcriptional programs. In parallel, emerging structural and biophysical studies reveal conformational plasticity and mechanosensitive properties that enable dynamic partitioning between adhesive and signaling pools. Disruption of these regulatory layers promotes tumor progression, metastasis, immune evasion, and therapy resistance, positioning β-catenin as both a central oncogenic node and a challenging therapeutic target. In this review, we integrate evolutionary, structural, and mechanobiological perspectives to illustrate how β-catenin exemplifies the double-edged nature of biological innovation, an ancient protein that enabled multicellular organization yet whose dysregulation underlies fundamental mechanisms of human cancer.},
}
RevDate: 2026-05-13
Beyond Genomes: Functional Signatures Reveal Evolutionary Patterns Across the Tree of Life.
Molecular biology and evolution pii:8677242 [Epub ahead of print].
Protein function evolution provides a powerful lens to uncover biological complexity. Here, we introduce the concept of the pan-functionome-the full set of protein functions encoded by the proteome of individuals belonging to a taxonomic group-and explore its evolutionary implications. By analyzing over 1,000 annotated proteomes across major branches of life, we identify systematic differences in functional composition that reflect deep evolutionary patterns. The number of biological processes per protein increases non-linearly over time, with functional diversification rather than protein expansion driving organismal complexity. Distinct taxonomic divisions invest differently in biological processes, highlighting signatures of multicellularity, metabolism, and stress response. Phylogenetic analyses suggest that the evolution of protein functions follows a non-neutral model. Furthermore, functional profiles allow robust taxonomic classification and reveal unique adaptations in individual organisms. Our findings suggest that the functionome provides a complementary perspective on evolution, with potential applications in taxonomy, evolutionary biology, and comparative genomics.
Additional Links: PMID-42126263
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42126263,
year = {2026},
author = {Muñoz-Mérida, A and Muñoz-Pajares, AJ},
title = {Beyond Genomes: Functional Signatures Reveal Evolutionary Patterns Across the Tree of Life.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msag121},
pmid = {42126263},
issn = {1537-1719},
abstract = {Protein function evolution provides a powerful lens to uncover biological complexity. Here, we introduce the concept of the pan-functionome-the full set of protein functions encoded by the proteome of individuals belonging to a taxonomic group-and explore its evolutionary implications. By analyzing over 1,000 annotated proteomes across major branches of life, we identify systematic differences in functional composition that reflect deep evolutionary patterns. The number of biological processes per protein increases non-linearly over time, with functional diversification rather than protein expansion driving organismal complexity. Distinct taxonomic divisions invest differently in biological processes, highlighting signatures of multicellularity, metabolism, and stress response. Phylogenetic analyses suggest that the evolution of protein functions follows a non-neutral model. Furthermore, functional profiles allow robust taxonomic classification and reveal unique adaptations in individual organisms. Our findings suggest that the functionome provides a complementary perspective on evolution, with potential applications in taxonomy, evolutionary biology, and comparative genomics.},
}
RevDate: 2026-05-11
CmpDate: 2026-05-11
Glioma-intrinsic SLC1A3 hijacks the vascular niche to establish an immunosuppressive microenvironment.
Frontiers in immunology, 17:1824726.
INTRODUCTION: Glioblastoma (GBM) is a highly lethal malignancy driven by glioma-initiating cells (GICs). While GICs are known to profoundly remodel tumor microenvironment (TME) to promote progression and immune evasion within the vascular niche, the specific transcriptomic reprogramming and alternative splicing events driving their evolution from neural stem cells (NSCs), and how these intrinsic cellular state changes dictate multi-cellular immunosuppressive networks and checkpoints, remain poorly understood. Unraveling these complex tumor-vascular-immune interactions is critical for identifying novel vulnerabilities and developing effective immunotherapies.
METHODS: To decode the GICs' evolutionary trajectory, we integrated RNA-seq and alternative splicing analysis of NSCs and patient-derived GIC cohorts. The malignant progression was mapped using scRNA-seq pseudotime analysis, and key targets were validated across clinical TCGA cohorts. Furthermore, we employed the large-scale single-cell foundation model, Geneformer, to perform in silico genetic perturbations, integrating it with interactome inference to decipher TME communication. Finally, the proposed tumor-endothelial-T cell multi-cellular axis was functionally validated utilizing in vitro tumor-HUVEC co-culture systems, qPCR, and FACS-based T cell activation (NFAT-Jurkat) assays.
RESULTS: Our multi-omics re-analysis identified extensive alternative splicing and transcriptional reprogramming during GICs evolution, pinpointing SLC1A3 as a core gene significantly upregulated along the malignant pseudotime trajectory and strongly correlated with poor clinical prognosis in GBM. AI-driven in silico virtual knockout utilizing Geneformer revealed that SLC1A3 acts as a master regulator of tumor network stability. Interactome analysis demonstrated that SLC1A3[hi] tumor cells exhibit intensive communication with endothelial cells via specific ligand-receptor axes (e.g., TNC-ITGB1, PTN-SDC3). In vitro assays confirmed that endothelial cells were educated by SLC1A3[hi] tumor cells that undergo malignant transition, drastically upregulating immune-suppressive factors, including CD274, TGFB1, IL10, and IDO1. Crucially, tumor-specific knockdown of SLC1A3 dismantled this vascular-immune suppressive niche, significantly restoring T cell activation in a multicellular co-culture model.
DISCUSSION: Our findings establish SLC1A3 not merely as an intrinsic driver of glioma development, but as a critical upstream node orchestrating a cascading tumor-endothelial-T cell immunosuppressive axis. By leveraging AI-based foundation models alongside robust biological validation, we uncovered a novel mechanism of vascular-mediated immune evasion, highlighting SLC1A3 as a highly promising therapeutic target to reprogram the glioblastoma microenvironment and restore anti-tumor immunity.
Additional Links: PMID-42112375
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42112375,
year = {2026},
author = {Lin, H and Liu, C and Chen, X and Zhao, Y and Lyu, Y and Zhang, B and Song, H and Fan, X and Li, S and He, Z and Yang, H and Mao, Y},
title = {Glioma-intrinsic SLC1A3 hijacks the vascular niche to establish an immunosuppressive microenvironment.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1824726},
pmid = {42112375},
issn = {1664-3224},
mesh = {Humans ; *Tumor Microenvironment/immunology ; *Glioma/immunology/pathology/genetics/metabolism ; *Brain Neoplasms/immunology/pathology/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Neoplastic Stem Cells/immunology/metabolism/pathology ; Alternative Splicing ; Neural Stem Cells/metabolism/immunology ; *Glioblastoma/immunology/pathology/genetics ; Cell Line, Tumor ; T-Lymphocytes/immunology ; },
abstract = {INTRODUCTION: Glioblastoma (GBM) is a highly lethal malignancy driven by glioma-initiating cells (GICs). While GICs are known to profoundly remodel tumor microenvironment (TME) to promote progression and immune evasion within the vascular niche, the specific transcriptomic reprogramming and alternative splicing events driving their evolution from neural stem cells (NSCs), and how these intrinsic cellular state changes dictate multi-cellular immunosuppressive networks and checkpoints, remain poorly understood. Unraveling these complex tumor-vascular-immune interactions is critical for identifying novel vulnerabilities and developing effective immunotherapies.
METHODS: To decode the GICs' evolutionary trajectory, we integrated RNA-seq and alternative splicing analysis of NSCs and patient-derived GIC cohorts. The malignant progression was mapped using scRNA-seq pseudotime analysis, and key targets were validated across clinical TCGA cohorts. Furthermore, we employed the large-scale single-cell foundation model, Geneformer, to perform in silico genetic perturbations, integrating it with interactome inference to decipher TME communication. Finally, the proposed tumor-endothelial-T cell multi-cellular axis was functionally validated utilizing in vitro tumor-HUVEC co-culture systems, qPCR, and FACS-based T cell activation (NFAT-Jurkat) assays.
RESULTS: Our multi-omics re-analysis identified extensive alternative splicing and transcriptional reprogramming during GICs evolution, pinpointing SLC1A3 as a core gene significantly upregulated along the malignant pseudotime trajectory and strongly correlated with poor clinical prognosis in GBM. AI-driven in silico virtual knockout utilizing Geneformer revealed that SLC1A3 acts as a master regulator of tumor network stability. Interactome analysis demonstrated that SLC1A3[hi] tumor cells exhibit intensive communication with endothelial cells via specific ligand-receptor axes (e.g., TNC-ITGB1, PTN-SDC3). In vitro assays confirmed that endothelial cells were educated by SLC1A3[hi] tumor cells that undergo malignant transition, drastically upregulating immune-suppressive factors, including CD274, TGFB1, IL10, and IDO1. Crucially, tumor-specific knockdown of SLC1A3 dismantled this vascular-immune suppressive niche, significantly restoring T cell activation in a multicellular co-culture model.
DISCUSSION: Our findings establish SLC1A3 not merely as an intrinsic driver of glioma development, but as a critical upstream node orchestrating a cascading tumor-endothelial-T cell immunosuppressive axis. By leveraging AI-based foundation models alongside robust biological validation, we uncovered a novel mechanism of vascular-mediated immune evasion, highlighting SLC1A3 as a highly promising therapeutic target to reprogram the glioblastoma microenvironment and restore anti-tumor immunity.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Tumor Microenvironment/immunology
*Glioma/immunology/pathology/genetics/metabolism
*Brain Neoplasms/immunology/pathology/genetics/metabolism
Gene Expression Regulation, Neoplastic
Neoplastic Stem Cells/immunology/metabolism/pathology
Alternative Splicing
Neural Stem Cells/metabolism/immunology
*Glioblastoma/immunology/pathology/genetics
Cell Line, Tumor
T-Lymphocytes/immunology
RevDate: 2026-05-09
Glycans in adhesion and fertilization: histochemical and ultrastructural insights from the chaetognath Spadella cephaloptera.
Frontiers in zoology pii:10.1186/s12983-026-00614-5 [Epub ahead of print].
BACKGROUND: To cope with the dynamic intertidal environment, some marine invertebrates have evolved carbohydrate-based adhesive mechanisms. Glycans are also involved in reproductive processes in protostomes, yet data about their distribution and function in chaetognaths are scarce. Among them, the benthic arrow worm Spadella cephaloptera can rapidly and temporarily attach to substrates, making it an interesting target for investigating the underlying glycobiology of its adhesion and reproductive systems. In this study, we characterized the distribution of different glycans in S. cephaloptera using histochemistry, immunofluorescence, lectin binding assays, and transmission electron microscopy, with a focus on the adhesive system during ontogeny.
RESULTS: Adhesive cells showed stage-specific distribution: in hatchlings, these cells form protrusions in the epidermis (papillae) and concentrate anteriorly, while in juveniles and adults, they group into multicellular adhesive cells forming clusters (compound papillae) in the posterior region. Ultrastructurally, the adhesive cells contain secretion granules enriched in fibrillar structures, and feature synaptic vesicles. Lectin binding revealed strong Peanut Agglutinin (PNA) affinity to the apical region of the cells, indicating the presence of Galβ1-3GalNAc moieties similar to other temporary adhesive systems. In addition, we detected acidic and sulfated mucosubstances in the sperm ducts, while a carboxylated jelly coat surrounds mature oocytes.
CONCLUSIONS: Our findings suggest that the ontogenetic shift of adhesive cells from the anterior to the posterior body region is correlated with the alimentary and foraging behavior during the life cycle of S. cephaloptera. Evidence from lectin-assays, histological stainings, and ultrastructural analyses reveals the involvement of glycans in both reproductive and adhesive systems, with patterns suggesting functional conservation of mechanisms present in other marine invertebrates. The observed glycan moieties in the adhesive cells of S. cephaloptera indicate convergently evolved traits, such as the presence of neutral mucosubstances and PNA-binding glycans, as reported for other temporary adhesive systems in marine invertebrates. This work provides a framework for a molecular characterization of the reproductive and adhesive systems of the enigmatic chaetognaths.
Additional Links: PMID-42106853
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42106853,
year = {2026},
author = {Barrera Grijalba, CC and Thetter-Dürr, S and Bibermair, J and Wollesen, T},
title = {Glycans in adhesion and fertilization: histochemical and ultrastructural insights from the chaetognath Spadella cephaloptera.},
journal = {Frontiers in zoology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12983-026-00614-5},
pmid = {42106853},
issn = {1742-9994},
abstract = {BACKGROUND: To cope with the dynamic intertidal environment, some marine invertebrates have evolved carbohydrate-based adhesive mechanisms. Glycans are also involved in reproductive processes in protostomes, yet data about their distribution and function in chaetognaths are scarce. Among them, the benthic arrow worm Spadella cephaloptera can rapidly and temporarily attach to substrates, making it an interesting target for investigating the underlying glycobiology of its adhesion and reproductive systems. In this study, we characterized the distribution of different glycans in S. cephaloptera using histochemistry, immunofluorescence, lectin binding assays, and transmission electron microscopy, with a focus on the adhesive system during ontogeny.
RESULTS: Adhesive cells showed stage-specific distribution: in hatchlings, these cells form protrusions in the epidermis (papillae) and concentrate anteriorly, while in juveniles and adults, they group into multicellular adhesive cells forming clusters (compound papillae) in the posterior region. Ultrastructurally, the adhesive cells contain secretion granules enriched in fibrillar structures, and feature synaptic vesicles. Lectin binding revealed strong Peanut Agglutinin (PNA) affinity to the apical region of the cells, indicating the presence of Galβ1-3GalNAc moieties similar to other temporary adhesive systems. In addition, we detected acidic and sulfated mucosubstances in the sperm ducts, while a carboxylated jelly coat surrounds mature oocytes.
CONCLUSIONS: Our findings suggest that the ontogenetic shift of adhesive cells from the anterior to the posterior body region is correlated with the alimentary and foraging behavior during the life cycle of S. cephaloptera. Evidence from lectin-assays, histological stainings, and ultrastructural analyses reveals the involvement of glycans in both reproductive and adhesive systems, with patterns suggesting functional conservation of mechanisms present in other marine invertebrates. The observed glycan moieties in the adhesive cells of S. cephaloptera indicate convergently evolved traits, such as the presence of neutral mucosubstances and PNA-binding glycans, as reported for other temporary adhesive systems in marine invertebrates. This work provides a framework for a molecular characterization of the reproductive and adhesive systems of the enigmatic chaetognaths.},
}
RevDate: 2026-05-08
CmpDate: 2026-05-08
Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components.
Frontiers in oncology, 16:1796428.
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive subtype of non-small cell lung cancer characterized by the coexistence of carcinomatous (CA) and sarcomatous (SA) components. Their clonal relationship and genomic divergence remain poorly defined, particularly in adenocarcinoma-derived PSC.
METHODS: We performed comparative whole-exome sequencing (WES) on microdissected CA and SA components from six pulmonary sarcomatoid adenocarcinomas (PSAdC). Histopathology and immunohistochemistry were used to characterize epithelial and mesenchymal phenotypes. Somatic mutations were identified using a standard bioinformatics pipeline, followed by gene set enrichment analysis with g:Profiler.
RESULTS: WES identified 133 non-synonymous variants across 34 genes (181 mutational events). Of these, 34.3% were shared, 29.3% were CA-specific, and 36.5% were SA-specific, indicating marked intratumor heterogeneity. Missense mutations predominated (71.4%). Recurrently altered genes included PCLO, CPS1, FAT1, PDE4DIP, and ARID1B, while canonical drivers TP53 and KRAS showed component-specific distributions. Enrichment analysis revealed over-representation of pathways related to multicellular organism development, chromatin remodeling, transcription factor binding, and DNA double-strand break repair, as well as non-small cell lung cancer signaling. These alterations correlated with epithelial-mesenchymal transition (EMT) features in SA components, including vimentin upregulation and E-cadherin loss.
CONCLUSIONS: PSAdC exhibits a monoclonal origin with subsequent genomic diversification between components. Microdissection-based WES reveals pronounced spatial heterogeneity and lineage-specific mutations. Dysregulated chromatin remodeling and DNA repair pathways, together with EMT-associated phenotypes, provide a mechanistic framework for sarcomatoid differentiation and lineage plasticity in this aggressive tumor subtype.
Additional Links: PMID-42100399
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid42100399,
year = {2026},
author = {Lin, J and Yang, Y and Liu, M and Yang, F and Jiang, S and Xu, L and Zheng, X and Wei, H and Wen, X and Xu, G and Weng, R and Zheng, J and Xiao, S},
title = {Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1796428},
pmid = {42100399},
issn = {2234-943X},
abstract = {BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive subtype of non-small cell lung cancer characterized by the coexistence of carcinomatous (CA) and sarcomatous (SA) components. Their clonal relationship and genomic divergence remain poorly defined, particularly in adenocarcinoma-derived PSC.
METHODS: We performed comparative whole-exome sequencing (WES) on microdissected CA and SA components from six pulmonary sarcomatoid adenocarcinomas (PSAdC). Histopathology and immunohistochemistry were used to characterize epithelial and mesenchymal phenotypes. Somatic mutations were identified using a standard bioinformatics pipeline, followed by gene set enrichment analysis with g:Profiler.
RESULTS: WES identified 133 non-synonymous variants across 34 genes (181 mutational events). Of these, 34.3% were shared, 29.3% were CA-specific, and 36.5% were SA-specific, indicating marked intratumor heterogeneity. Missense mutations predominated (71.4%). Recurrently altered genes included PCLO, CPS1, FAT1, PDE4DIP, and ARID1B, while canonical drivers TP53 and KRAS showed component-specific distributions. Enrichment analysis revealed over-representation of pathways related to multicellular organism development, chromatin remodeling, transcription factor binding, and DNA double-strand break repair, as well as non-small cell lung cancer signaling. These alterations correlated with epithelial-mesenchymal transition (EMT) features in SA components, including vimentin upregulation and E-cadherin loss.
CONCLUSIONS: PSAdC exhibits a monoclonal origin with subsequent genomic diversification between components. Microdissection-based WES reveals pronounced spatial heterogeneity and lineage-specific mutations. Dysregulated chromatin remodeling and DNA repair pathways, together with EMT-associated phenotypes, provide a mechanistic framework for sarcomatoid differentiation and lineage plasticity in this aggressive tumor subtype.},
}
RevDate: 2022-10-12
CmpDate: 2022-09-15
Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria.
Molecular biology and evolution, 39(9):.
Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth's biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.
Additional Links: PMID-35946347
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35946347,
year = {2022},
author = {Chen, MY and Teng, WK and Zhao, L and Han, BP and Song, LR and Shu, WS},
title = {Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria.},
journal = {Molecular biology and evolution},
volume = {39},
number = {9},
pages = {},
pmid = {35946347},
issn = {1537-1719},
mesh = {*Cyanobacteria/genetics ; Gene Transfer, Horizontal ; Nitrogen/metabolism ; *Nitrogen Fixation/genetics ; Photosynthesis/genetics ; Phylogeny ; },
abstract = {Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth's biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Cyanobacteria/genetics
Gene Transfer, Horizontal
Nitrogen/metabolism
*Nitrogen Fixation/genetics
Photosynthesis/genetics
Phylogeny
RevDate: 2025-10-31
CmpDate: 2022-08-12
4-bit adhesion logic enables universal multicellular interface patterning.
Nature, 608(7922):324-329.
Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].
Additional Links: PMID-35948712
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35948712,
year = {2022},
author = {Kim, H and Skinner, DJ and Glass, DS and Hamby, AE and Stuart, BAR and Dunkel, J and Riedel-Kruse, IH},
title = {4-bit adhesion logic enables universal multicellular interface patterning.},
journal = {Nature},
volume = {608},
number = {7922},
pages = {324-329},
pmid = {35948712},
issn = {1476-4687},
support = {R01 GM145893/GM/NIGMS NIH HHS/United States ; },
mesh = {*Algorithms ; *Artificial Cells/cytology ; Biofilms ; *Cell Adhesion ; Humans ; *Logic ; *Synthetic Biology/methods ; },
abstract = {Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Algorithms
*Artificial Cells/cytology
Biofilms
*Cell Adhesion
Humans
*Logic
*Synthetic Biology/methods
RevDate: 2024-02-14
CmpDate: 2022-10-04
Evolution of fungal phenotypic disparity.
Nature ecology & evolution, 6(10):1489-1500.
Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.
Additional Links: PMID-35970862
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35970862,
year = {2022},
author = {Smith, TJ and Donoghue, PCJ},
title = {Evolution of fungal phenotypic disparity.},
journal = {Nature ecology & evolution},
volume = {6},
number = {10},
pages = {1489-1500},
pmid = {35970862},
issn = {2397-334X},
support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Animals ; *Biological Evolution ; *Fungi/genetics ; Phenotype ; Plants ; },
abstract = {Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Biological Evolution
*Fungi/genetics
Phenotype
Plants
RevDate: 2025-10-08
CmpDate: 2022-08-18
Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.
Medical oncology (Northwood, London, England), 39(11):160.
The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.
Additional Links: PMID-35972622
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35972622,
year = {2022},
author = {Jacques, F and Baratchart, E and Pienta, KJ and Hammarlund, EU},
title = {Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.},
journal = {Medical oncology (Northwood, London, England)},
volume = {39},
number = {11},
pages = {160},
pmid = {35972622},
issn = {1559-131X},
support = {U01 CA143055/CA/NCI NIH HHS/United States ; CA163124/CA/NCI NIH HHS/United States ; 949538/ERC_/European Research Council/International ; U54 CA143803/CA/NCI NIH HHS/United States ; CA143055/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; U54 CA163124/CA/NCI NIH HHS/United States ; P01 CA093900/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Differentiation/genetics ; Eukaryota/genetics ; *Neoplasms/genetics ; Phylogeny ; },
abstract = {The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Biological Evolution
Cell Communication
Cell Differentiation/genetics
Eukaryota/genetics
*Neoplasms/genetics
Phylogeny
RevDate: 2025-07-28
CmpDate: 2022-09-15
Tradeoff breaking as a model of evolutionary transitions in individuality and limits of the fitness-decoupling metaphor.
eLife, 11:.
Evolutionary transitions in individuality (ETIs) involve the formation of Darwinian collectives from Darwinian particles. The transition from cells to multicellular life is a prime example. During an ETI, collectives become units of selection in their own right. However, the underlying processes are poorly understood. One observation used to identify the completion of an ETI is an increase in collective-level performance accompanied by a decrease in particle-level performance, for example measured by growth rate. This seemingly counterintuitive dynamic has been referred to as fitness decoupling and has been used to interpret both models and experimental data. Extending and unifying results from the literature, we show that fitness of particles and collectives can never decouple because calculations of fitness performed over appropriate and equivalent time intervals are necessarily the same provided the population reaches a stable collective size distribution. By way of solution, we draw attention to the value of mechanistic approaches that emphasise traits, and tradeoffs among traits, as opposed to fitness. This trait-based approach is sufficient to capture dynamics that underpin evolutionary transitions. In addition, drawing upon both experimental and theoretical studies, we show that while early stages of transitions might often involve tradeoffs among particle traits, later-and critical-stages are likely to involve the rupture of such tradeoffs. Thus, when observed in the context of ETIs, tradeoff-breaking events stand as a useful marker of these transitions.
Additional Links: PMID-35975712
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35975712,
year = {2022},
author = {Bourrat, P and Doulcier, G and Rose, CJ and Rainey, PB and Hammerschmidt, K},
title = {Tradeoff breaking as a model of evolutionary transitions in individuality and limits of the fitness-decoupling metaphor.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35975712},
issn = {2050-084X},
mesh = {*Biological Evolution ; *Metaphor ; Phenotype ; Selection, Genetic ; },
abstract = {Evolutionary transitions in individuality (ETIs) involve the formation of Darwinian collectives from Darwinian particles. The transition from cells to multicellular life is a prime example. During an ETI, collectives become units of selection in their own right. However, the underlying processes are poorly understood. One observation used to identify the completion of an ETI is an increase in collective-level performance accompanied by a decrease in particle-level performance, for example measured by growth rate. This seemingly counterintuitive dynamic has been referred to as fitness decoupling and has been used to interpret both models and experimental data. Extending and unifying results from the literature, we show that fitness of particles and collectives can never decouple because calculations of fitness performed over appropriate and equivalent time intervals are necessarily the same provided the population reaches a stable collective size distribution. By way of solution, we draw attention to the value of mechanistic approaches that emphasise traits, and tradeoffs among traits, as opposed to fitness. This trait-based approach is sufficient to capture dynamics that underpin evolutionary transitions. In addition, drawing upon both experimental and theoretical studies, we show that while early stages of transitions might often involve tradeoffs among particle traits, later-and critical-stages are likely to involve the rupture of such tradeoffs. Thus, when observed in the context of ETIs, tradeoff-breaking events stand as a useful marker of these transitions.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Biological Evolution
*Metaphor
Phenotype
Selection, Genetic
RevDate: 2022-10-24
CmpDate: 2022-10-03
Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1α (AhR/HIF-1α) signaling: Impact on the aging process.
Cellular signalling, 99:110445.
The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for environmental toxins and UV radiation but also for many endogenous ligands, e.g., L-tryptophan metabolites. The AhR signaling system is evolutionarily conserved and AhR homologs existed as many as 600 million years ago. The ancient atmosphere demanded the evolution of an oxygen-sensing system, i.e., hypoxia-inducible transcription factors (HIF) and their prolyl hydroxylase regulators (PHD). Given that both signaling systems have important roles in embryogenesis, it seems that they have been involved in the evolution of multicellular organisms. The evolutionary origin of the aging process is unknown although it is most likely associated with the evolution of multicellularity. Intriguingly, there is compelling evidence that while HIF-1α signaling extends the lifespan, that of AhR promotes many age-related degenerative processes, e.g., it increases oxidative stress, inhibits autophagy, promotes cellular senescence, and aggravates extracellular matrix degeneration. In contrast, HIF-1α signaling stimulates autophagy, inhibits cellular senescence, and enhances cell proliferation. Interestingly, there is a clear antagonism between the AhR and HIF-1α signaling pathways. For instance, (i) AhR and HIF-1α factors heterodimerize with the same factor, ARNT/HIF-1β, leading to their competition for DNA-binding, (ii) AhR and HIF-1α signaling exert antagonistic effects on autophagy, and (iii) co-chaperone p23 exhibits specific functions in the signaling of AhR and HIF-1α factors. One might speculate that it is the competition between the AhR and HIF-1α signaling pathways that is a driving force in the aging process.
Additional Links: PMID-35988806
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35988806,
year = {2022},
author = {Salminen, A},
title = {Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1α (AhR/HIF-1α) signaling: Impact on the aging process.},
journal = {Cellular signalling},
volume = {99},
number = {},
pages = {110445},
doi = {10.1016/j.cellsig.2022.110445},
pmid = {35988806},
issn = {1873-3913},
mesh = {DNA ; *Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Oxygen ; Prolyl Hydroxylases ; Pyridinolcarbamate ; *Receptors, Aryl Hydrocarbon/genetics/metabolism ; Tryptophan ; },
abstract = {The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for environmental toxins and UV radiation but also for many endogenous ligands, e.g., L-tryptophan metabolites. The AhR signaling system is evolutionarily conserved and AhR homologs existed as many as 600 million years ago. The ancient atmosphere demanded the evolution of an oxygen-sensing system, i.e., hypoxia-inducible transcription factors (HIF) and their prolyl hydroxylase regulators (PHD). Given that both signaling systems have important roles in embryogenesis, it seems that they have been involved in the evolution of multicellular organisms. The evolutionary origin of the aging process is unknown although it is most likely associated with the evolution of multicellularity. Intriguingly, there is compelling evidence that while HIF-1α signaling extends the lifespan, that of AhR promotes many age-related degenerative processes, e.g., it increases oxidative stress, inhibits autophagy, promotes cellular senescence, and aggravates extracellular matrix degeneration. In contrast, HIF-1α signaling stimulates autophagy, inhibits cellular senescence, and enhances cell proliferation. Interestingly, there is a clear antagonism between the AhR and HIF-1α signaling pathways. For instance, (i) AhR and HIF-1α factors heterodimerize with the same factor, ARNT/HIF-1β, leading to their competition for DNA-binding, (ii) AhR and HIF-1α signaling exert antagonistic effects on autophagy, and (iii) co-chaperone p23 exhibits specific functions in the signaling of AhR and HIF-1α factors. One might speculate that it is the competition between the AhR and HIF-1α signaling pathways that is a driving force in the aging process.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
DNA
*Hypoxia-Inducible Factor 1, alpha Subunit/genetics
Oxygen
Prolyl Hydroxylases
Pyridinolcarbamate
*Receptors, Aryl Hydrocarbon/genetics/metabolism
Tryptophan
RevDate: 2025-10-31
CmpDate: 2022-08-24
Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.
Nature communications, 13(1):4853.
Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.
Additional Links: PMID-35995772
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35995772,
year = {2022},
author = {Nyongesa, S and Weber, PM and Bernet, È and Pulido, F and Nieves, C and Nieckarz, M and Delaby, M and Viehboeck, T and Krause, N and Rivera-Millot, A and Nakamura, A and Vischer, NOE and vanNieuwenhze, M and Brun, YV and Cava, F and Bulgheresi, S and Veyrier, FJ},
title = {Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {4853},
pmid = {35995772},
issn = {2041-1723},
support = {DOC 69/FWF_/Austrian Science Fund FWF/Austria ; P 28593/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Cell Division ; Cell Wall/metabolism ; Mammals/microbiology ; *Neisseriaceae/cytology ; Peptidoglycan/metabolism ; },
abstract = {Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Bacterial Proteins/genetics/metabolism
Biological Evolution
*Cell Division
Cell Wall/metabolism
Mammals/microbiology
*Neisseriaceae/cytology
Peptidoglycan/metabolism
RevDate: 2025-07-28
CmpDate: 2022-08-25
A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.
BMC biology, 20(1):184.
BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.
RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.
CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.
Additional Links: PMID-35999597
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid35999597,
year = {2022},
author = {Gahan, JM and Leclère, L and Hernandez-Valladares, M and Rentzsch, F},
title = {A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.},
journal = {BMC biology},
volume = {20},
number = {1},
pages = {184},
pmid = {35999597},
issn = {1741-7007},
mesh = {Animals ; Cell Differentiation ; *Chromatin ; Histone Demethylases/genetics ; Mammals/genetics ; Phylogeny ; *Sea Anemones/metabolism ; },
abstract = {BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.
RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.
CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Cell Differentiation
*Chromatin
Histone Demethylases/genetics
Mammals/genetics
Phylogeny
*Sea Anemones/metabolism
RevDate: 2025-07-28
CmpDate: 2022-08-26
[Advances in the plant multicellular network analysis].
Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 38(8):2798-2810.
Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.
Additional Links: PMID-36002411
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36002411,
year = {2022},
author = {Shi, B and Huang, X and Fu, X and Wang, B},
title = {[Advances in the plant multicellular network analysis].},
journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology},
volume = {38},
number = {8},
pages = {2798-2810},
doi = {10.13345/j.cjb.220127},
pmid = {36002411},
issn = {1872-2075},
mesh = {*Plants ; },
abstract = {Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Plants
RevDate: 2022-11-01
CmpDate: 2022-09-23
Divergent genomic trajectories predate the origin of animals and fungi.
Nature, 609(7928):747-753.
Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.
Additional Links: PMID-36002568
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36002568,
year = {2022},
author = {Ocaña-Pallarès, E and Williams, TA and López-Escardó, D and Arroyo, AS and Pathmanathan, JS and Bapteste, E and Tikhonenkov, DV and Keeling, PJ and Szöllősi, GJ and Ruiz-Trillo, I},
title = {Divergent genomic trajectories predate the origin of animals and fungi.},
journal = {Nature},
volume = {609},
number = {7928},
pages = {747-753},
pmid = {36002568},
issn = {1476-4687},
support = {616960/ERC_/European Research Council/International ; 714774/ERC_/European Research Council/International ; 615274/ERC_/European Research Council/International ; },
mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Genes ; *Genome/genetics ; Genome, Fungal/genetics ; *Genomics ; Metabolism/genetics ; *Phylogeny ; },
abstract = {Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Evolution, Molecular
*Fungi/genetics
Gene Transfer, Horizontal
Genes
*Genome/genetics
Genome, Fungal/genetics
*Genomics
Metabolism/genetics
*Phylogeny
RevDate: 2025-07-28
CmpDate: 2022-08-29
A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.
Genes, 13(8):.
Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.
Additional Links: PMID-36011312
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36011312,
year = {2022},
author = {Le, NG and van Ulsen, P and van Spanning, R and Brouwer, A and van Straalen, NM and Roelofs, D},
title = {A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.},
journal = {Genes},
volume = {13},
number = {8},
pages = {},
pmid = {36011312},
issn = {2073-4425},
mesh = {Animals ; *Arthropods/genetics ; Bacteria/genetics ; Carbohydrates ; Escherichia coli/genetics ; Eukaryota ; *Gene Transfer, Horizontal ; Insecta ; Protein Sorting Signals/genetics ; Soil ; },
abstract = {Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Arthropods/genetics
Bacteria/genetics
Carbohydrates
Escherichia coli/genetics
Eukaryota
*Gene Transfer, Horizontal
Insecta
Protein Sorting Signals/genetics
Soil
RevDate: 2024-09-03
Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.
Microorganisms, 10(8):.
Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.
Additional Links: PMID-36013944
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36013944,
year = {2022},
author = {Guryanova, SV},
title = {Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.},
journal = {Microorganisms},
volume = {10},
number = {8},
pages = {},
pmid = {36013944},
issn = {2076-2607},
abstract = {Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.},
}
RevDate: 2025-07-28
CmpDate: 2022-09-13
Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.
Experimental cell research, 419(2):113317.
Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.
Additional Links: PMID-36028058
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36028058,
year = {2022},
author = {Senthilkumar, I and Howley, E and McEvoy, E},
title = {Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.},
journal = {Experimental cell research},
volume = {419},
number = {2},
pages = {113317},
doi = {10.1016/j.yexcr.2022.113317},
pmid = {36028058},
issn = {1090-2422},
mesh = {Computer Simulation ; Humans ; *Models, Biological ; *Neoplasms ; Tumor Microenvironment ; },
abstract = {Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Computer Simulation
Humans
*Models, Biological
*Neoplasms
Tumor Microenvironment
RevDate: 2022-08-30
Virtual spherical-shaped multicellular platform for simulating the morphogenetic processes of spider-like body axis formation.
Frontiers in cell and developmental biology, 10:932814.
Remodeling of multicellular architecture is a critical developmental process for shaping the axis of a bilaterally symmetric animal body and involves coordinated cell-cell interactions and cell rearrangement. In arthropods, the early embryonic process that leads to the segmented body axis varies at the cellular and molecular levels depending on the species. Developmental studies using insect and spider model species have provided specific examples of these diversified mechanisms that regulate axis formation and segmentation in arthropod embryos. However, there are few theoretical models for how diversity in the early embryonic process occurred during evolution, in part because of a limited computational infrastructure. We developed a virtual spherical-shaped multicellular platform to reproduce body axis-forming processes. Each virtual cell behaves according to the cell vertex model, with the computational program organized in a hierarchical order from cells and tissues to whole embryos. Using an initial set of two different mechanical states for cell differentiation and global directional signals that are linked to the planar polarity of each cell, the virtual cell assembly exhibited morphogenetic processes similar to those observed in spider embryos. We found that the development of an elongating body axis is achieved through implementation of an interactive cell polarity parameter associated with edge tension at the cell-cell adhesion interface, with no local control of the cell division rate and direction. We also showed that modifying the settings can cause variation in morphogenetic processes. This platform also can embed a gene network that generates waves of gene expression in a virtual dynamic multicellular field. This study provides a computational platform for testing the development and evolution of animal body patterns.
Additional Links: PMID-36036016
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36036016,
year = {2022},
author = {Fujiwara, M and Akiyama-Oda, Y and Oda, H},
title = {Virtual spherical-shaped multicellular platform for simulating the morphogenetic processes of spider-like body axis formation.},
journal = {Frontiers in cell and developmental biology},
volume = {10},
number = {},
pages = {932814},
pmid = {36036016},
issn = {2296-634X},
abstract = {Remodeling of multicellular architecture is a critical developmental process for shaping the axis of a bilaterally symmetric animal body and involves coordinated cell-cell interactions and cell rearrangement. In arthropods, the early embryonic process that leads to the segmented body axis varies at the cellular and molecular levels depending on the species. Developmental studies using insect and spider model species have provided specific examples of these diversified mechanisms that regulate axis formation and segmentation in arthropod embryos. However, there are few theoretical models for how diversity in the early embryonic process occurred during evolution, in part because of a limited computational infrastructure. We developed a virtual spherical-shaped multicellular platform to reproduce body axis-forming processes. Each virtual cell behaves according to the cell vertex model, with the computational program organized in a hierarchical order from cells and tissues to whole embryos. Using an initial set of two different mechanical states for cell differentiation and global directional signals that are linked to the planar polarity of each cell, the virtual cell assembly exhibited morphogenetic processes similar to those observed in spider embryos. We found that the development of an elongating body axis is achieved through implementation of an interactive cell polarity parameter associated with edge tension at the cell-cell adhesion interface, with no local control of the cell division rate and direction. We also showed that modifying the settings can cause variation in morphogenetic processes. This platform also can embed a gene network that generates waves of gene expression in a virtual dynamic multicellular field. This study provides a computational platform for testing the development and evolution of animal body patterns.},
}
RevDate: 2026-01-27
CmpDate: 2022-10-28
Symbiosis between Candidatus Patescibacteria and Archaea Discovered in Wastewater-Treating Bioreactors.
mBio, 13(5):e0171122.
Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized by their ultrasmall cell size and symbiotic lifestyles (potentially commensal, mutualistic, and parasitic relationships), namely, Candidatus Patescibacteria (also known as the Candidate Phyla Radiation/CPR superphylum) and DPANN archaea, respectively. Cultivation-based approaches have revealed that Ca. Patescibacteria and DPANN symbiotically interact with bacterial and archaeal partners and hosts, respectively, but that cross-domain symbiosis and parasitism have never been observed. By amending wastewater treatment sludge samples with methanogenic archaea, we observed increased abundances of Ca. Patescibacteria (Ca. Yanofskybacteria/UBA5738) and, using fluorescence in situ hybridization (FISH), discovered that nearly all of the Ca. Yanofskybacteria/UBA5738 cells were attached to Methanothrix (95.7 ± 2.1%) and that none of the cells were attached to other lineages, implying high host dependency and specificity. Methanothrix filaments (multicellular) with Ca. Yanofskybacteria/UBA5738 attached had significantly more cells with no or low detectable ribosomal activity (based on FISH fluorescence) and often showed deformations at the sites of attachment (based on transmission electron microscopy), suggesting that the interaction is parasitic. Metagenome-assisted metabolic reconstruction showed that Ca. Yanofskybacteria/UBA5738 lacks most of the biosynthetic pathways necessary for cell growth and universally conserves three unique gene arrays that contain multiple genes with signal peptides in the metagenome-assembled genomes of the Ca. Yanofskybacteria/UBA5738 lineage. The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR and DPANN. IMPORTANCE One highly diverse phylogenetic group of Bacteria, Ca. Patescibacteria, remains poorly understood, but, from the few cultured representatives and metagenomic investigations, they are thought to live symbiotically or parasitically with other bacteria or even with eukarya. We explored the possibility of symbiotic interactions with Archaea by amending wastewater treatment sludge samples that were rich in Ca. Patescibacteria and Archaea with an isolate archaeon that is closely related to a methanogen population abundant in situ (Methanothrix). This strategic cultivation successfully established enrichment cultures that were mainly comprised of Ca. Patescibacteria (family level lineage Ca. Yanofskybacteria/UBA5738) and Methanothrix, in which we found highly specific physical interactions between the two organisms. Microscopic observations based on transmission electron microscopy, target-specific fluorescence in situ hybridization, and metagenomic analyses showed evidence that the interaction is likely parasitic. The results show a novel cross-domain parasitism between Bacteria and Archaea and suggest that the amendment of host Archaea may be an effective approach in culturing novel Ca. Patescibacteria.
Additional Links: PMID-36043790
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36043790,
year = {2022},
author = {Kuroda, K and Yamamoto, K and Nakai, R and Hirakata, Y and Kubota, K and Nobu, MK and Narihiro, T},
title = {Symbiosis between Candidatus Patescibacteria and Archaea Discovered in Wastewater-Treating Bioreactors.},
journal = {mBio},
volume = {13},
number = {5},
pages = {e0171122},
pmid = {36043790},
issn = {2150-7511},
mesh = {*Archaea/metabolism ; Symbiosis/genetics ; Wastewater ; Phylogeny ; In Situ Hybridization, Fluorescence ; Sewage ; Bacteria/genetics ; *Euryarchaeota ; Bioreactors ; Protein Sorting Signals/genetics ; },
abstract = {Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized by their ultrasmall cell size and symbiotic lifestyles (potentially commensal, mutualistic, and parasitic relationships), namely, Candidatus Patescibacteria (also known as the Candidate Phyla Radiation/CPR superphylum) and DPANN archaea, respectively. Cultivation-based approaches have revealed that Ca. Patescibacteria and DPANN symbiotically interact with bacterial and archaeal partners and hosts, respectively, but that cross-domain symbiosis and parasitism have never been observed. By amending wastewater treatment sludge samples with methanogenic archaea, we observed increased abundances of Ca. Patescibacteria (Ca. Yanofskybacteria/UBA5738) and, using fluorescence in situ hybridization (FISH), discovered that nearly all of the Ca. Yanofskybacteria/UBA5738 cells were attached to Methanothrix (95.7 ± 2.1%) and that none of the cells were attached to other lineages, implying high host dependency and specificity. Methanothrix filaments (multicellular) with Ca. Yanofskybacteria/UBA5738 attached had significantly more cells with no or low detectable ribosomal activity (based on FISH fluorescence) and often showed deformations at the sites of attachment (based on transmission electron microscopy), suggesting that the interaction is parasitic. Metagenome-assisted metabolic reconstruction showed that Ca. Yanofskybacteria/UBA5738 lacks most of the biosynthetic pathways necessary for cell growth and universally conserves three unique gene arrays that contain multiple genes with signal peptides in the metagenome-assembled genomes of the Ca. Yanofskybacteria/UBA5738 lineage. The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR and DPANN. IMPORTANCE One highly diverse phylogenetic group of Bacteria, Ca. Patescibacteria, remains poorly understood, but, from the few cultured representatives and metagenomic investigations, they are thought to live symbiotically or parasitically with other bacteria or even with eukarya. We explored the possibility of symbiotic interactions with Archaea by amending wastewater treatment sludge samples that were rich in Ca. Patescibacteria and Archaea with an isolate archaeon that is closely related to a methanogen population abundant in situ (Methanothrix). This strategic cultivation successfully established enrichment cultures that were mainly comprised of Ca. Patescibacteria (family level lineage Ca. Yanofskybacteria/UBA5738) and Methanothrix, in which we found highly specific physical interactions between the two organisms. Microscopic observations based on transmission electron microscopy, target-specific fluorescence in situ hybridization, and metagenomic analyses showed evidence that the interaction is likely parasitic. The results show a novel cross-domain parasitism between Bacteria and Archaea and suggest that the amendment of host Archaea may be an effective approach in culturing novel Ca. Patescibacteria.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Archaea/metabolism
Symbiosis/genetics
Wastewater
Phylogeny
In Situ Hybridization, Fluorescence
Sewage
Bacteria/genetics
*Euryarchaeota
Bioreactors
Protein Sorting Signals/genetics
RevDate: 2023-02-03
CmpDate: 2022-11-30
Food for thought - ILC metabolism in the context of helminth infections.
Mucosal immunology, 15(6):1234-1242.
Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.
Additional Links: PMID-36045216
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36045216,
year = {2022},
author = {Michla, M and Wilhelm, C},
title = {Food for thought - ILC metabolism in the context of helminth infections.},
journal = {Mucosal immunology},
volume = {15},
number = {6},
pages = {1234-1242},
pmid = {36045216},
issn = {1935-3456},
mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; *Helminthiasis ; *Helminths ; Inflammation ; },
abstract = {Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Humans
Immunity, Innate
Lymphocytes
*Helminthiasis
*Helminths
Inflammation
RevDate: 2022-12-14
CmpDate: 2022-10-27
A phylogenomically informed five-order system for the closest relatives of land plants.
Current biology : CB, 32(20):4473-4482.e7.
The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.
Additional Links: PMID-36055238
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36055238,
year = {2022},
author = {Hess, S and Williams, SK and Busch, A and Irisarri, I and Delwiche, CF and de Vries, S and Darienko, T and Roger, AJ and Archibald, JM and Buschmann, H and von Schwartzenberg, K and de Vries, J},
title = {A phylogenomically informed five-order system for the closest relatives of land plants.},
journal = {Current biology : CB},
volume = {32},
number = {20},
pages = {4473-4482.e7},
pmid = {36055238},
issn = {1879-0445},
mesh = {Phylogeny ; Biological Evolution ; *Embryophyta/genetics ; *Charophyceae/genetics ; *Streptophyta ; Plants ; Soil ; },
abstract = {The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Phylogeny
Biological Evolution
*Embryophyta/genetics
*Charophyceae/genetics
*Streptophyta
Plants
Soil
RevDate: 2022-09-28
CmpDate: 2022-09-28
Competition for finite resources as coordination mechanism for morphogenesis: An evolutionary algorithm study of digital embryogeny.
Bio Systems, 221:104762.
The standard view of embryogenesis is one of cooperation driven by the cells' shared genetics and evolutionary interests. However, numerous examples from developmental biology and agriculture reveal a surprising amount of competition among body cells, tissues, and organs for both metabolic and informational resources. To explain the existence of such competition we had hypothesized that evolution uses limiting "reservoirs" of resource molecules as a communication medium - a global scratchpad, to enable tissues across the body to coordinate growth. Here, we test this hypothesis via an evolutionary simulation of embryogeny in silico. Genomes encode state transition rules for cells, such as proliferation, differentiation, and resource use, enabling virtual embryos to develop a specific large-scale morphology. An evolutionary algorithm operates over the genomes, with fitness defined as a function of specific morphological requirements for the final embryo shape. We found that not only does such an algorithm rapidly discover rules for cellular behavior that reliably make embryos with specific anatomical properties, but that it discovers the strategy of using finite resources to coordinate development. Given the option of using finite or infinite reservoirs (which determine cells' ability to carry out specific actions), evolution preferentially uses finite reservoirs, which results in higher fitness and increased consistency (without needing direct selection for morphological invariance). We report aspects of anatomical, physiological/transcriptional, and genomic analysis of evolved virtual embryos that help understand how evolution can use competition among genetically identical subunits within a multicellular body to coordinate reliable, complex morphogenesis. Our results suggest that under some conditions, composite multi-scale systems will promote conflict and artificial scarcity for their components.
Additional Links: PMID-36064151
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36064151,
year = {2022},
author = {Smiley, P and Levin, M},
title = {Competition for finite resources as coordination mechanism for morphogenesis: An evolutionary algorithm study of digital embryogeny.},
journal = {Bio Systems},
volume = {221},
number = {},
pages = {104762},
doi = {10.1016/j.biosystems.2022.104762},
pmid = {36064151},
issn = {1872-8324},
mesh = {Algorithms ; *Biological Evolution ; Computer Simulation ; *Embryonic Development/genetics ; Morphogenesis/genetics ; },
abstract = {The standard view of embryogenesis is one of cooperation driven by the cells' shared genetics and evolutionary interests. However, numerous examples from developmental biology and agriculture reveal a surprising amount of competition among body cells, tissues, and organs for both metabolic and informational resources. To explain the existence of such competition we had hypothesized that evolution uses limiting "reservoirs" of resource molecules as a communication medium - a global scratchpad, to enable tissues across the body to coordinate growth. Here, we test this hypothesis via an evolutionary simulation of embryogeny in silico. Genomes encode state transition rules for cells, such as proliferation, differentiation, and resource use, enabling virtual embryos to develop a specific large-scale morphology. An evolutionary algorithm operates over the genomes, with fitness defined as a function of specific morphological requirements for the final embryo shape. We found that not only does such an algorithm rapidly discover rules for cellular behavior that reliably make embryos with specific anatomical properties, but that it discovers the strategy of using finite resources to coordinate development. Given the option of using finite or infinite reservoirs (which determine cells' ability to carry out specific actions), evolution preferentially uses finite reservoirs, which results in higher fitness and increased consistency (without needing direct selection for morphological invariance). We report aspects of anatomical, physiological/transcriptional, and genomic analysis of evolved virtual embryos that help understand how evolution can use competition among genetically identical subunits within a multicellular body to coordinate reliable, complex morphogenesis. Our results suggest that under some conditions, composite multi-scale systems will promote conflict and artificial scarcity for their components.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Algorithms
*Biological Evolution
Computer Simulation
*Embryonic Development/genetics
Morphogenesis/genetics
RevDate: 2025-07-28
CmpDate: 2022-09-12
Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).
International journal of molecular sciences, 23(17):.
Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.
Additional Links: PMID-36076976
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36076976,
year = {2022},
author = {Burzacka-Hinz, A and Narajczyk, M and Dudek, M and Szlachetko, DL},
title = {Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).},
journal = {International journal of molecular sciences},
volume = {23},
number = {17},
pages = {},
pmid = {36076976},
issn = {1422-0067},
mesh = {*Dendrobium ; Flowers/anatomy & histology ; Microscopy, Electron, Scanning ; *Orchidaceae/anatomy & histology ; Phylogeny ; Trichomes ; },
abstract = {Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Dendrobium
Flowers/anatomy & histology
Microscopy, Electron, Scanning
*Orchidaceae/anatomy & histology
Phylogeny
Trichomes
RevDate: 2025-07-28
CmpDate: 2022-09-12
Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.
International journal of molecular sciences, 23(17):.
Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.
Additional Links: PMID-36077092
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36077092,
year = {2022},
author = {Anatskaya, OV and Vinogradov, AE},
title = {Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.},
journal = {International journal of molecular sciences},
volume = {23},
number = {17},
pages = {},
pmid = {36077092},
issn = {1422-0067},
support = {Agreement No. 075-15-2021-1075, signed 28 September 2021//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Chromatin ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; *Polyploidy ; Proto-Oncogenes ; },
abstract = {Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Chromatin
Epigenesis, Genetic
*Gene Regulatory Networks
Humans
*Polyploidy
Proto-Oncogenes
RevDate: 2024-09-04
Genomic and Epigenomic Characterization of Tumor Organoid Models.
Cancers, 14(17):.
Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene-drug interactions and genotype-phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research.
Additional Links: PMID-36077628
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36077628,
year = {2022},
author = {Nam, C and Ziman, B and Sheth, M and Zhao, H and Lin, DC},
title = {Genomic and Epigenomic Characterization of Tumor Organoid Models.},
journal = {Cancers},
volume = {14},
number = {17},
pages = {},
pmid = {36077628},
issn = {2072-6694},
support = {P30 CA014089/CA/NCI NIH HHS/United States ; R37 CA237022/CA/NCI NIH HHS/United States ; P30CA014089/CA/NCI NIH HHS/United States ; R37CA237022/NH/NIH HHS/United States ; },
abstract = {Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene-drug interactions and genotype-phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research.},
}
RevDate: 2024-09-18
CmpDate: 2022-12-23
Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.
mSystems, 7(5):e0056222.
The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.
Additional Links: PMID-36098425
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36098425,
year = {2022},
author = {Noh, S and Capodanno, BJ and Xu, S and Hamilton, MC and Strassmann, JE and Queller, DC},
title = {Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.},
journal = {mSystems},
volume = {7},
number = {5},
pages = {e0056222},
pmid = {36098425},
issn = {2379-5077},
support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; P20GM103423//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {Animals ; *Amoeba/microbiology ; *Dictyostelium/genetics ; Eukaryota ; *Burkholderiaceae/genetics ; Bacteria/genetics ; Soil ; },
abstract = {The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Amoeba/microbiology
*Dictyostelium/genetics
Eukaryota
*Burkholderiaceae/genetics
Bacteria/genetics
Soil
RevDate: 2024-09-04
CmpDate: 2022-09-15
Eco-evolutionary dynamics of clonal multicellular life cycles.
eLife, 11:.
The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.
Additional Links: PMID-36099169
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36099169,
year = {2022},
author = {Ress, V and Traulsen, A and Pichugin, Y},
title = {Eco-evolutionary dynamics of clonal multicellular life cycles.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {36099169},
issn = {2050-084X},
mesh = {Animals ; *Biological Evolution ; *Life Cycle Stages ; Models, Theoretical ; },
abstract = {The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Biological Evolution
*Life Cycle Stages
Models, Theoretical
RevDate: 2022-12-14
CmpDate: 2022-11-21
A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.
The New phytologist, 236(6):2294-2310.
Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.
Additional Links: PMID-36102042
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36102042,
year = {2022},
author = {Xie, Q and Xiong, C and Yang, Q and Zheng, F and Larkin, RM and Zhang, J and Wang, T and Zhang, Y and Ouyang, B and Lu, Y and Ye, J and Ye, Z and Yang, C},
title = {A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.},
journal = {The New phytologist},
volume = {236},
number = {6},
pages = {2294-2310},
doi = {10.1111/nph.18492},
pmid = {36102042},
issn = {1469-8137},
mesh = {*Trichomes/metabolism ; *Solanum lycopersicum/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Plant Epidermis/metabolism ; },
abstract = {Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Trichomes/metabolism
*Solanum lycopersicum/genetics/metabolism
Gene Expression Regulation, Plant
Plant Proteins/genetics/metabolism
Plant Epidermis/metabolism
RevDate: 2022-10-18
CmpDate: 2022-09-16
Resident cardiac macrophages: Heterogeneity and function in health and disease.
Immunity, 55(9):1549-1563.
Understanding tissue macrophage biology has become challenging in recent years due the ever-increasing complexity in macrophage-subset identification and functional characterization. This is particularly important within the myocardium, as we have come to understand that macrophages play multifaceted roles in cardiac health and disease, and heart disease remains the leading cause of death worldwide. Here, we review recent progress in the field, focusing on resident cardiac macrophage heterogeneity, origins, and functions at steady state and after injury. We stratify resident cardiac macrophage functions by the ability of macrophages to either directly influence cardiac physiology or indirectly influence cardiac physiology through orchestrating multi-cellular communication with cardiomyocytes and stromal and immune populations.
Additional Links: PMID-36103852
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36103852,
year = {2022},
author = {Zaman, R and Epelman, S},
title = {Resident cardiac macrophages: Heterogeneity and function in health and disease.},
journal = {Immunity},
volume = {55},
number = {9},
pages = {1549-1563},
doi = {10.1016/j.immuni.2022.08.009},
pmid = {36103852},
issn = {1097-4180},
mesh = {*Heart/physiology ; *Macrophages ; Myocardium ; },
abstract = {Understanding tissue macrophage biology has become challenging in recent years due the ever-increasing complexity in macrophage-subset identification and functional characterization. This is particularly important within the myocardium, as we have come to understand that macrophages play multifaceted roles in cardiac health and disease, and heart disease remains the leading cause of death worldwide. Here, we review recent progress in the field, focusing on resident cardiac macrophage heterogeneity, origins, and functions at steady state and after injury. We stratify resident cardiac macrophage functions by the ability of macrophages to either directly influence cardiac physiology or indirectly influence cardiac physiology through orchestrating multi-cellular communication with cardiomyocytes and stromal and immune populations.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Heart/physiology
*Macrophages
Myocardium
RevDate: 2022-09-17
Evolving social behavior through selection of single-cell adhesion in Dictyostelium discoideum.
iScience, 25(9):105006.
The social amoeba Dictyostelium discoideum commonly forms chimeric fruiting bodies. Genetic variants that produce a higher proportion of spores are predicted to undercut multicellular organization unless cooperators assort positively. Cell adhesion is considered a primary factor driving such assortment, but evolution of adhesion has not been experimentally connected to changes in social performance. We modified by experimental evolution the efficiency of individual cells in attaching to a surface. Surprisingly, evolution appears to have produced social cooperators irrespective of whether stronger or weaker adhesion was selected. Quantification of reproductive success, cell-cell adhesion, and developmental patterns, however, revealed two distinct social behaviors, as captured when the classical metric for social success is generalized by considering clonal spore production. Our work shows that cell mechanical interactions can constrain the evolution of development and sociality in chimeras and that elucidation of proximate mechanisms is necessary to understand the ultimate emergence of multicellular organization.
Additional Links: PMID-36105585
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36105585,
year = {2022},
author = {Adiba, S and Forget, M and De Monte, S},
title = {Evolving social behavior through selection of single-cell adhesion in Dictyostelium discoideum.},
journal = {iScience},
volume = {25},
number = {9},
pages = {105006},
pmid = {36105585},
issn = {2589-0042},
abstract = {The social amoeba Dictyostelium discoideum commonly forms chimeric fruiting bodies. Genetic variants that produce a higher proportion of spores are predicted to undercut multicellular organization unless cooperators assort positively. Cell adhesion is considered a primary factor driving such assortment, but evolution of adhesion has not been experimentally connected to changes in social performance. We modified by experimental evolution the efficiency of individual cells in attaching to a surface. Surprisingly, evolution appears to have produced social cooperators irrespective of whether stronger or weaker adhesion was selected. Quantification of reproductive success, cell-cell adhesion, and developmental patterns, however, revealed two distinct social behaviors, as captured when the classical metric for social success is generalized by considering clonal spore production. Our work shows that cell mechanical interactions can constrain the evolution of development and sociality in chimeras and that elucidation of proximate mechanisms is necessary to understand the ultimate emergence of multicellular organization.},
}
RevDate: 2022-09-17
RrTTG1 promotes fruit prickle development through an MBW complex in Rosa roxburghii.
Frontiers in plant science, 13:939270.
Fruit prickles are widely distributed on the pericarp and exhibit polymorphic traits at different developmental stages. Although they are multicellular appendages that are well-known for helping plants defend against biotic and abiotic stresses, their origination and molecular mechanism are still less known. Here, we studied the origination and molecular mechanism of fruit prickles in Rosa roxburghii. Using morphological and histological observations, we found that the fruit prickle primordium of R. roxburghii originated from the ground meristem that underwent cell division to form flagelliform prickles, continued to enlarge, and finally lignified to form mature fruit prickles. We amplified a homolog of candidate gene TRANSPARENT TESTA GLABRA1 (TTG1) from R. roxburghii, named RrTTG1. RrTTG1 harbored four conserved WD-repeat domains and was exclusively nuclear-localized. Using qRT-PCR and in situ hybridization, we found that RrTTG1 was constitutively expressed and highly expressed during the initiation and cell expansion phases of fruit prickles. Ectopic expression analysis in Arabidopsis proved that RrTTG1 substantially enhanced the number of trichome and pigmentation production and inhibited root hair formation. Besides, RrTTG1 complemented the phenotypes of the ttg1 mutant in Arabidopsis, thus indicating that RrTTG1 played pleiotropic roles akin to AtTTG1. We demonstrated that the RrTTG1 only interacted with RrEGL3, a homolog of ENHANCER OF GLABRA3 (EGL3), via yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Briefly, RrTTG1 might positively regulate the initiation of fruit prickle primordium and cell enlargement by forming the RrTTG1-RrEGL3-RrGL1 complex in R. roxburghii. Therefore, our results help characterize the RrTTG1 in R. roxburghii and also elucidate the establishment of the prickles regulatory system in the Rosaceae plants.
Additional Links: PMID-36105707
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36105707,
year = {2022},
author = {Huang, X and Yi, P and Liu, Y and Li, Q and Jiang, Y and Yi, Y and Yan, H},
title = {RrTTG1 promotes fruit prickle development through an MBW complex in Rosa roxburghii.},
journal = {Frontiers in plant science},
volume = {13},
number = {},
pages = {939270},
pmid = {36105707},
issn = {1664-462X},
abstract = {Fruit prickles are widely distributed on the pericarp and exhibit polymorphic traits at different developmental stages. Although they are multicellular appendages that are well-known for helping plants defend against biotic and abiotic stresses, their origination and molecular mechanism are still less known. Here, we studied the origination and molecular mechanism of fruit prickles in Rosa roxburghii. Using morphological and histological observations, we found that the fruit prickle primordium of R. roxburghii originated from the ground meristem that underwent cell division to form flagelliform prickles, continued to enlarge, and finally lignified to form mature fruit prickles. We amplified a homolog of candidate gene TRANSPARENT TESTA GLABRA1 (TTG1) from R. roxburghii, named RrTTG1. RrTTG1 harbored four conserved WD-repeat domains and was exclusively nuclear-localized. Using qRT-PCR and in situ hybridization, we found that RrTTG1 was constitutively expressed and highly expressed during the initiation and cell expansion phases of fruit prickles. Ectopic expression analysis in Arabidopsis proved that RrTTG1 substantially enhanced the number of trichome and pigmentation production and inhibited root hair formation. Besides, RrTTG1 complemented the phenotypes of the ttg1 mutant in Arabidopsis, thus indicating that RrTTG1 played pleiotropic roles akin to AtTTG1. We demonstrated that the RrTTG1 only interacted with RrEGL3, a homolog of ENHANCER OF GLABRA3 (EGL3), via yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Briefly, RrTTG1 might positively regulate the initiation of fruit prickle primordium and cell enlargement by forming the RrTTG1-RrEGL3-RrGL1 complex in R. roxburghii. Therefore, our results help characterize the RrTTG1 in R. roxburghii and also elucidate the establishment of the prickles regulatory system in the Rosaceae plants.},
}
RevDate: 2022-12-09
CmpDate: 2022-09-20
Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.
Communications biology, 5(1):977.
Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.
Additional Links: PMID-36114258
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36114258,
year = {2022},
author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ},
title = {Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {977},
pmid = {36114258},
issn = {2399-3642},
mesh = {Agar ; Animals ; *Myxococcus xanthus/genetics ; Phenotype ; *Predatory Behavior ; },
abstract = {Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Agar
Animals
*Myxococcus xanthus/genetics
Phenotype
*Predatory Behavior
RevDate: 2022-09-30
CmpDate: 2022-09-23
A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.
BMC biology, 20(1):199.
BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.
RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.
CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.
Additional Links: PMID-36127662
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36127662,
year = {2022},
author = {Chai, S and Aria, C and Hua, H},
title = {A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.},
journal = {BMC biology},
volume = {20},
number = {1},
pages = {199},
pmid = {36127662},
issn = {1741-7007},
mesh = {Animals ; China ; *Chlorophyta/genetics ; *Ecosystem ; Eukaryotic Cells ; Fossils ; },
abstract = {BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.
RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.
CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
China
*Chlorophyta/genetics
*Ecosystem
Eukaryotic Cells
Fossils
RevDate: 2023-11-05
Bioselectivity of silk protein-based materials and their bio-inspired applications.
Beilstein journal of nanotechnology, 13:902-921.
Adhesion to material surfaces is crucial for almost all organisms regarding subsequent biological responses. Mammalian cell attachment to a surrounding biological matrix is essential for maintaining their survival and function concerning tissue formation. Conversely, the adhesion and presence of microbes interferes with important multicellular processes of tissue development. Therefore, tailoring bioselective, biologically active, and multifunctional materials for biomedical applications is a modern focus of biomaterial research. Engineering biomaterials that stimulate and interact with cell receptors to support binding and subsequent physiological responses of multicellular systems attracted much interest in the last years. Further to this, the increasing threat of multidrug resistance of pathogens against antibiotics to human health urgently requires new material concepts for preventing microbial infestation and biofilm formation. Thus, materials exhibiting microbial repellence or antimicrobial behaviour to reduce inflammation, while selectively enhancing regeneration in host tissues are of utmost interest. In this context, protein-based materials are interesting candidates due to their natural origin, biological activity, and structural properties. Silk materials, in particular those made of spider silk proteins and their recombinant counterparts, are characterized by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses on biological processes and surface interactions involved in the bioselective adhesion of mammalian cells and repellence of microbes on protein-based material surfaces. In addition, it highlights the importance of materials made of recombinant spider silk proteins, focussing on the progress regarding bioselectivity.
Additional Links: PMID-36127898
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36127898,
year = {2022},
author = {Bargel, H and Trossmann, VT and Sommer, C and Scheibel, T},
title = {Bioselectivity of silk protein-based materials and their bio-inspired applications.},
journal = {Beilstein journal of nanotechnology},
volume = {13},
number = {},
pages = {902-921},
pmid = {36127898},
issn = {2190-4286},
abstract = {Adhesion to material surfaces is crucial for almost all organisms regarding subsequent biological responses. Mammalian cell attachment to a surrounding biological matrix is essential for maintaining their survival and function concerning tissue formation. Conversely, the adhesion and presence of microbes interferes with important multicellular processes of tissue development. Therefore, tailoring bioselective, biologically active, and multifunctional materials for biomedical applications is a modern focus of biomaterial research. Engineering biomaterials that stimulate and interact with cell receptors to support binding and subsequent physiological responses of multicellular systems attracted much interest in the last years. Further to this, the increasing threat of multidrug resistance of pathogens against antibiotics to human health urgently requires new material concepts for preventing microbial infestation and biofilm formation. Thus, materials exhibiting microbial repellence or antimicrobial behaviour to reduce inflammation, while selectively enhancing regeneration in host tissues are of utmost interest. In this context, protein-based materials are interesting candidates due to their natural origin, biological activity, and structural properties. Silk materials, in particular those made of spider silk proteins and their recombinant counterparts, are characterized by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses on biological processes and surface interactions involved in the bioselective adhesion of mammalian cells and repellence of microbes on protein-based material surfaces. In addition, it highlights the importance of materials made of recombinant spider silk proteins, focussing on the progress regarding bioselectivity.},
}
RevDate: 2022-09-24
Synthetic Extracellular Matrices for 3D Culture of Schwann Cells, Hepatocytes, and HUVECs.
Bioengineering (Basel, Switzerland), 9(9):.
Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.
Additional Links: PMID-36134999
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36134999,
year = {2022},
author = {Ma, C and Liu, K and Li, Q and Xiong, Y and Xu, C and Zhang, W and Ruan, C and Li, X and Lei, X},
title = {Synthetic Extracellular Matrices for 3D Culture of Schwann Cells, Hepatocytes, and HUVECs.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {9},
number = {9},
pages = {},
pmid = {36134999},
issn = {2306-5354},
support = {2021YFA0719303//National Key Research and Development Program of China/ ; 81901058, 81900686//National Natural Science Foundation of China/ ; 2022A1515010952//Natural Science Foundation of Guangdong Province/ ; JCYJ20210324115814040//Shenzhen Fundamental Research Foundation/ ; },
abstract = {Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.},
}
RevDate: 2022-09-28
CmpDate: 2022-09-26
Innate Immunity Mechanisms in Marine Multicellular Organisms.
Marine drugs, 20(9):.
The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body's homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology.
Additional Links: PMID-36135738
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36135738,
year = {2022},
author = {Guryanova, SV and Ovchinnikova, TV},
title = {Innate Immunity Mechanisms in Marine Multicellular Organisms.},
journal = {Marine drugs},
volume = {20},
number = {9},
pages = {},
pmid = {36135738},
issn = {1660-3397},
support = {22-14-00380//Russian Science Foundation/ ; },
mesh = {*Immunity, Innate ; Receptors, Pattern Recognition/metabolism ; *Signal Transduction ; },
abstract = {The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body's homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Immunity, Innate
Receptors, Pattern Recognition/metabolism
*Signal Transduction
RevDate: 2024-09-04
Cancer and Chaos and the Complex Network Model of a Multicellular Organism.
Biology, 11(9):.
In the search of theoretical models describing cancer, one of promising directions is chaos. It is connected to ideas of "genome chaos" and "life on the edge of chaos", but they profoundly differ in the meaning of the term "chaos". To build any coherent models, notions used by both ideas should be firstly brought closer. The hypothesis "life on the edge of chaos" using deterministic chaos has been radically deepened developed in recent years by the discovery of half-chaos. This new view requires a deeper interpretation within the range of the cell and the organism. It has impacts on understanding "chaos" in the term "genome chaos". This study intends to present such an interpretation on the basis of which such searches will be easier and closer to intuition. We interpret genome chaos as deterministic chaos in a large module of half-chaotic network modeling the cell. We observed such chaotic modules in simulations of evolution controlled by weaker variant of natural selection. We also discuss differences between free and somatic cells in modeling their disturbance using half-chaotic networks.
Additional Links: PMID-36138796
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36138796,
year = {2022},
author = {Gecow, A and Iantovics, LB and Tez, M},
title = {Cancer and Chaos and the Complex Network Model of a Multicellular Organism.},
journal = {Biology},
volume = {11},
number = {9},
pages = {},
pmid = {36138796},
issn = {2079-7737},
abstract = {In the search of theoretical models describing cancer, one of promising directions is chaos. It is connected to ideas of "genome chaos" and "life on the edge of chaos", but they profoundly differ in the meaning of the term "chaos". To build any coherent models, notions used by both ideas should be firstly brought closer. The hypothesis "life on the edge of chaos" using deterministic chaos has been radically deepened developed in recent years by the discovery of half-chaos. This new view requires a deeper interpretation within the range of the cell and the organism. It has impacts on understanding "chaos" in the term "genome chaos". This study intends to present such an interpretation on the basis of which such searches will be easier and closer to intuition. We interpret genome chaos as deterministic chaos in a large module of half-chaotic network modeling the cell. We observed such chaotic modules in simulations of evolution controlled by weaker variant of natural selection. We also discuss differences between free and somatic cells in modeling their disturbance using half-chaotic networks.},
}
RevDate: 2022-09-24
Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis.
iScience, 25(10):105034.
Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors. We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort. This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.
Additional Links: PMID-36147948
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36147948,
year = {2022},
author = {Boutry, J and Tissot, S and Mekaoui, N and Dujon, A and Meliani, J and Hamede, R and Ujvari, B and Roche, B and Nedelcu, AM and Tokolyi, J and Thomas, F},
title = {Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis.},
journal = {iScience},
volume = {25},
number = {10},
pages = {105034},
pmid = {36147948},
issn = {2589-0042},
abstract = {Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors. We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort. This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.},
}
RevDate: 2023-04-15
CmpDate: 2022-12-20
Microbial succession in a marine sediment: Inferring interspecific microbial interactions with marine cable bacteria.
Environmental microbiology, 24(12):6348-6364.
Cable bacteria are long, filamentous, multicellular bacteria that grow in marine sediments and couple sulfide oxidation to oxygen reduction over centimetre-scale distances via long-distance electron transport. Cable bacteria can strongly modify biogeochemical cycling and may affect microbial community networks. Here we examine interspecific interactions with marine cable bacteria (Ca. Electrothrix) by monitoring the succession of 16S rRNA amplicons (DNA and RNA) and cell abundance across depth and time, contrasting sediments with and without cable bacteria growth. In the oxic zone, cable bacteria activity was positively associated with abundant predatory bacteria (Bdellovibrionota, Myxococcota, Bradymonadales), indicating putative predation on cathodic cells. At suboxic depths, cable bacteria activity was positively associated with sulfate-reducing and magnetotactic bacteria, consistent with cable bacteria functioning as ecosystem engineers that modify their local biogeochemical environment, benefitting certain microbes. Cable bacteria activity was negatively associated with chemoautotrophic sulfur-oxidizing Gammaproteobacteria (Thiogranum, Sedimenticola) at oxic depths, suggesting competition, and positively correlated with these taxa at suboxic depths, suggesting syntrophy and/or facilitation. These observations are consistent with chemoautotrophic sulfur oxidizers benefitting from an oxidizing potential imparted by cable bacteria at suboxic depths, possibly by using cable bacteria as acceptors for electrons or electron equivalents, but by an as yet enigmatic mechanism.
Additional Links: PMID-36178156
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36178156,
year = {2022},
author = {Liau, P and Kim, C and Saxton, MA and Malkin, SY},
title = {Microbial succession in a marine sediment: Inferring interspecific microbial interactions with marine cable bacteria.},
journal = {Environmental microbiology},
volume = {24},
number = {12},
pages = {6348-6364},
pmid = {36178156},
issn = {1462-2920},
mesh = {RNA, Ribosomal, 16S/genetics ; Oxidation-Reduction ; Geologic Sediments/microbiology ; *Deltaproteobacteria/genetics ; Bacteria/genetics ; Sulfur ; *Gammaproteobacteria/genetics ; *Microbiota ; Microbial Interactions ; Phylogeny ; },
abstract = {Cable bacteria are long, filamentous, multicellular bacteria that grow in marine sediments and couple sulfide oxidation to oxygen reduction over centimetre-scale distances via long-distance electron transport. Cable bacteria can strongly modify biogeochemical cycling and may affect microbial community networks. Here we examine interspecific interactions with marine cable bacteria (Ca. Electrothrix) by monitoring the succession of 16S rRNA amplicons (DNA and RNA) and cell abundance across depth and time, contrasting sediments with and without cable bacteria growth. In the oxic zone, cable bacteria activity was positively associated with abundant predatory bacteria (Bdellovibrionota, Myxococcota, Bradymonadales), indicating putative predation on cathodic cells. At suboxic depths, cable bacteria activity was positively associated with sulfate-reducing and magnetotactic bacteria, consistent with cable bacteria functioning as ecosystem engineers that modify their local biogeochemical environment, benefitting certain microbes. Cable bacteria activity was negatively associated with chemoautotrophic sulfur-oxidizing Gammaproteobacteria (Thiogranum, Sedimenticola) at oxic depths, suggesting competition, and positively correlated with these taxa at suboxic depths, suggesting syntrophy and/or facilitation. These observations are consistent with chemoautotrophic sulfur oxidizers benefitting from an oxidizing potential imparted by cable bacteria at suboxic depths, possibly by using cable bacteria as acceptors for electrons or electron equivalents, but by an as yet enigmatic mechanism.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
RNA, Ribosomal, 16S/genetics
Oxidation-Reduction
Geologic Sediments/microbiology
*Deltaproteobacteria/genetics
Bacteria/genetics
Sulfur
*Gammaproteobacteria/genetics
*Microbiota
Microbial Interactions
Phylogeny
RevDate: 2024-09-23
CmpDate: 2023-05-16
Fiber density and matrix stiffness modulate distinct cell migration modes in a 3D stroma mimetic composite hydrogel.
Acta biomaterialia, 163:378-391.
The peritumoral stroma is a complex 3D tissue that provides cells with myriad biophysical and biochemical cues. Histologic observations suggest that during metastatic spread of carcinomas, these cues influence transformed epithelial cells, prompting a diversity of migration modes spanning single cell and multicellular phenotypes. Purported consequences of these variations in tumor escape strategies include differential metastatic capability and therapy resistance. Therefore, understanding how cues from the peritumoral stromal microenvironment regulate migration mode has both prognostic and therapeutic value. Here, we utilize a synthetic stromal mimetic in which matrix fiber density and bulk hydrogel mechanics can be orthogonally tuned to investigate the contribution of these two key matrix attributes on MCF10A migration mode phenotypes, epithelial-mesenchymal transition (EMT), and invasive potential. We develop an automated computational image analysis framework to extract migratory phenotypes from fluorescent images and determine 3D migration metrics relevant to metastatic spread. Using this analysis, we find that matrix fiber density and bulk hydrogel mechanics distinctly contribute to a variety of MCF10A migration modes including amoeboid, single mesenchymal, clusters, and strands. We identify combinations of physical and soluble cues that induce a variety of migration modes originating from the same MCF10A spheroid and use these settings to examine a functional consequence of migration mode -resistance to apoptosis. We find that cells migrating as strands are more resistant to staurosporine-induced apoptosis than either disconnected clusters or individual invading cells. Improved models of the peritumoral stromal microenvironment and understanding of the relationships between matrix attributes and cell migration mode can aid ongoing efforts to identify effective cancer therapeutics that address cell plasticity-based therapy resistances. STATEMENT OF SIGNIFICANCE: Stromal extracellular matrix structure dictates both cell homeostasis and activation towards migratory phenotypes. However decoupling the effects of myriad biophysical cues has been difficult to achieve. Here, we encapsulate electrospun fiber segments within an amorphous hydrogel to create a fiber-reinforced hydrogel composite in which fiber density and hydrogel stiffness can be orthogonally tuned. Quantification of 3D cell migration reveal these two parameters uniquely contribute to a diversity of migration phenotypes spanning amoeboid, single mesenchymal, multicellular cluster, and collective strand. By tuning biophysical and biochemical cues to elicit heterogeneous migration phenotypes, we find that collective strands best resist apoptosis. This work establishes a composite approach to modulate fibrous topography and bulk hydrogel mechanics and identified biomaterial parameters to direct distinct 3D cell migration phenotypes.
Additional Links: PMID-36179980
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36179980,
year = {2023},
author = {Hiraki, HL and Matera, DL and Wang, WY and Prabhu, ES and Zhang, Z and Midekssa, F and Argento, AE and Buschhaus, JM and Humphries, BA and Luker, GD and Pena-Francesch, A and Baker, BM},
title = {Fiber density and matrix stiffness modulate distinct cell migration modes in a 3D stroma mimetic composite hydrogel.},
journal = {Acta biomaterialia},
volume = {163},
number = {},
pages = {378-391},
pmid = {36179980},
issn = {1878-7568},
support = {R50 CA221807/CA/NCI NIH HHS/United States ; R01 CA238042/CA/NCI NIH HHS/United States ; R01 CA238023/CA/NCI NIH HHS/United States ; R00 HL124322/HL/NHLBI NIH HHS/United States ; R01 EB030474/EB/NIBIB NIH HHS/United States ; R33 CA225549/CA/NCI NIH HHS/United States ; K99 HL124322/HL/NHLBI NIH HHS/United States ; U01 CA210152/CA/NCI NIH HHS/United States ; R37 CA222563/CA/NCI NIH HHS/United States ; T32 DE007057/DE/NIDCR NIH HHS/United States ; R01 CA196018/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Hydrogels/pharmacology/chemistry ; Cell Movement ; *Neoplasms ; Biocompatible Materials/pharmacology ; Epithelial Cells ; Extracellular Matrix ; Tumor Microenvironment ; },
abstract = {The peritumoral stroma is a complex 3D tissue that provides cells with myriad biophysical and biochemical cues. Histologic observations suggest that during metastatic spread of carcinomas, these cues influence transformed epithelial cells, prompting a diversity of migration modes spanning single cell and multicellular phenotypes. Purported consequences of these variations in tumor escape strategies include differential metastatic capability and therapy resistance. Therefore, understanding how cues from the peritumoral stromal microenvironment regulate migration mode has both prognostic and therapeutic value. Here, we utilize a synthetic stromal mimetic in which matrix fiber density and bulk hydrogel mechanics can be orthogonally tuned to investigate the contribution of these two key matrix attributes on MCF10A migration mode phenotypes, epithelial-mesenchymal transition (EMT), and invasive potential. We develop an automated computational image analysis framework to extract migratory phenotypes from fluorescent images and determine 3D migration metrics relevant to metastatic spread. Using this analysis, we find that matrix fiber density and bulk hydrogel mechanics distinctly contribute to a variety of MCF10A migration modes including amoeboid, single mesenchymal, clusters, and strands. We identify combinations of physical and soluble cues that induce a variety of migration modes originating from the same MCF10A spheroid and use these settings to examine a functional consequence of migration mode -resistance to apoptosis. We find that cells migrating as strands are more resistant to staurosporine-induced apoptosis than either disconnected clusters or individual invading cells. Improved models of the peritumoral stromal microenvironment and understanding of the relationships between matrix attributes and cell migration mode can aid ongoing efforts to identify effective cancer therapeutics that address cell plasticity-based therapy resistances. STATEMENT OF SIGNIFICANCE: Stromal extracellular matrix structure dictates both cell homeostasis and activation towards migratory phenotypes. However decoupling the effects of myriad biophysical cues has been difficult to achieve. Here, we encapsulate electrospun fiber segments within an amorphous hydrogel to create a fiber-reinforced hydrogel composite in which fiber density and hydrogel stiffness can be orthogonally tuned. Quantification of 3D cell migration reveal these two parameters uniquely contribute to a diversity of migration phenotypes spanning amoeboid, single mesenchymal, multicellular cluster, and collective strand. By tuning biophysical and biochemical cues to elicit heterogeneous migration phenotypes, we find that collective strands best resist apoptosis. This work establishes a composite approach to modulate fibrous topography and bulk hydrogel mechanics and identified biomaterial parameters to direct distinct 3D cell migration phenotypes.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Hydrogels/pharmacology/chemistry
Cell Movement
*Neoplasms
Biocompatible Materials/pharmacology
Epithelial Cells
Extracellular Matrix
Tumor Microenvironment
RevDate: 2022-10-04
CmpDate: 2022-10-04
The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.
Biochemistry. Biokhimiia, 87(9):916-931.
Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.
Additional Links: PMID-36180988
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36180988,
year = {2022},
author = {Turishcheva, E and Vildanova, M and Onishchenko, G and Smirnova, E},
title = {The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.},
journal = {Biochemistry. Biokhimiia},
volume = {87},
number = {9},
pages = {916-931},
pmid = {36180988},
issn = {1608-3040},
mesh = {*COVID-19 ; Cell Differentiation ; *Endoplasmic Reticulum Stress ; Fibrosis ; Humans ; Unfolded Protein Response ; },
abstract = {Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*COVID-19
Cell Differentiation
*Endoplasmic Reticulum Stress
Fibrosis
Humans
Unfolded Protein Response
RevDate: 2025-10-08
CmpDate: 2022-10-06
Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.
Open biology, 12(10):220146.
Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.
Additional Links: PMID-36196535
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36196535,
year = {2022},
author = {Gauthier, AE and Rotjan, RD and Kagan, JC},
title = {Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.},
journal = {Open biology},
volume = {12},
number = {10},
pages = {220146},
pmid = {36196535},
issn = {2046-2441},
support = {R01 AI093589/AI/NIAID NIH HHS/United States ; R56 AI093589/AI/NIAID NIH HHS/United States ; R37 AI116550/AI/NIAID NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; U19 AI133524/AI/NIAID NIH HHS/United States ; R01 AI116550/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; Immune System/metabolism ; Immunity, Innate ; *Lipopolysaccharides ; Mammals ; *Pathogen-Associated Molecular Pattern Molecules ; },
abstract = {Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Immune System/metabolism
Immunity, Innate
*Lipopolysaccharides
Mammals
*Pathogen-Associated Molecular Pattern Molecules
RevDate: 2022-11-01
CmpDate: 2022-11-01
Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.
Progress in biophysics and molecular biology, 175:131-139.
Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.
Additional Links: PMID-36198374
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36198374,
year = {2022},
author = {Grunt, TW and Valent, P},
title = {Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.},
journal = {Progress in biophysics and molecular biology},
volume = {175},
number = {},
pages = {131-139},
doi = {10.1016/j.pbiomolbio.2022.09.009},
pmid = {36198374},
issn = {1873-1732},
mesh = {Humans ; *Biological Evolution ; Thermodynamics ; Entropy ; *Neoplasms ; Mutation ; },
abstract = {Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Biological Evolution
Thermodynamics
Entropy
*Neoplasms
Mutation
RevDate: 2022-10-07
Biological activities of meroterpenoids isolated from different sources.
Frontiers in pharmacology, 13:830103.
Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.
Additional Links: PMID-36199687
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36199687,
year = {2022},
author = {Fuloria, NK and Raheja, RK and Shah, KH and Oza, MJ and Kulkarni, YA and Subramaniyan, V and Sekar, M and Fuloria, S},
title = {Biological activities of meroterpenoids isolated from different sources.},
journal = {Frontiers in pharmacology},
volume = {13},
number = {},
pages = {830103},
pmid = {36199687},
issn = {1663-9812},
abstract = {Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.},
}
RevDate: 2022-12-22
CmpDate: 2022-11-15
Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.
Journal of controlled release : official journal of the Controlled Release Society, 351:941-953.
Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.
Additional Links: PMID-36202151
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36202151,
year = {2022},
author = {Wang, P and Chen, C and Wang, Q and Chen, H and Chen, C and Xu, J and Wang, X and Song, T},
title = {Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {351},
number = {},
pages = {941-953},
doi = {10.1016/j.jconrel.2022.09.059},
pmid = {36202151},
issn = {1873-4995},
mesh = {Animals ; *Magnetosomes/metabolism ; Gram-Negative Bacteria ; Bacteria/metabolism ; Magnetics ; Mammals ; },
abstract = {Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Magnetosomes/metabolism
Gram-Negative Bacteria
Bacteria/metabolism
Magnetics
Mammals
RevDate: 2023-03-01
Age-related somatic mutation burden in human tissues.
Frontiers in aging, 3:1018119.
The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. De novo mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.
Additional Links: PMID-36213345
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36213345,
year = {2022},
author = {Ren, P and Dong, X and Vijg, J},
title = {Age-related somatic mutation burden in human tissues.},
journal = {Frontiers in aging},
volume = {3},
number = {},
pages = {1018119},
pmid = {36213345},
issn = {2673-6217},
support = {P01 AG017242/AG/NIA NIH HHS/United States ; },
abstract = {The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. De novo mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.},
}
RevDate: 2022-10-17
CmpDate: 2022-10-12
Novel multicellular prokaryote discovered next to an underground stream.
eLife, 11:.
A diversity of prokaryotes currently exhibit multicellularity with different generation mechanisms in a variety of contexts of ecology on Earth. In the present study, we report a new type of multicellular bacterium, HS-3, isolated from an underground stream. HS-3 self-organizes its filamentous cells into a layer-structured colony with the properties of a nematic liquid crystal. After maturation, the colony starts to form a semi-closed sphere accommodating clusters of coccobacillus daughter cells and selectively releases them upon contact with water. This is the first report that shows that a liquid-crystal status of cells can support the prokaryotic multicellular behavior. Importantly, the observed behavior of HS-3 suggests that the recurrent intermittent exposure of colonies to water flow in the cave might have been the ecological context that cultivated the evolutionary transition from unicellular to multicellular life. This is the new extant model that underpins theories regarding a role of ecological context in the emergence of multicellularity.
Additional Links: PMID-36217817
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36217817,
year = {2022},
author = {Mizuno, K and Maree, M and Nagamura, T and Koga, A and Hirayama, S and Furukawa, S and Tanaka, K and Morikawa, K},
title = {Novel multicellular prokaryote discovered next to an underground stream.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {36217817},
issn = {2050-084X},
mesh = {*Biological Evolution ; *Groundwater ; Pralidoxime Compounds ; Water ; },
abstract = {A diversity of prokaryotes currently exhibit multicellularity with different generation mechanisms in a variety of contexts of ecology on Earth. In the present study, we report a new type of multicellular bacterium, HS-3, isolated from an underground stream. HS-3 self-organizes its filamentous cells into a layer-structured colony with the properties of a nematic liquid crystal. After maturation, the colony starts to form a semi-closed sphere accommodating clusters of coccobacillus daughter cells and selectively releases them upon contact with water. This is the first report that shows that a liquid-crystal status of cells can support the prokaryotic multicellular behavior. Importantly, the observed behavior of HS-3 suggests that the recurrent intermittent exposure of colonies to water flow in the cave might have been the ecological context that cultivated the evolutionary transition from unicellular to multicellular life. This is the new extant model that underpins theories regarding a role of ecological context in the emergence of multicellularity.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Biological Evolution
*Groundwater
Pralidoxime Compounds
Water
RevDate: 2023-11-06
CmpDate: 2022-10-12
Illuminating a new path to multicellularity.
eLife, 11:.
A new species of multicellular bacteria broadens our understanding of prokaryotic multicellularity and provides insight into how multicellular organisms arise.
Additional Links: PMID-36217823
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36217823,
year = {2022},
author = {Datta, S and Ratcliff, WC},
title = {Illuminating a new path to multicellularity.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {36217823},
issn = {2050-084X},
support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; },
mesh = {*Biological Evolution ; },
abstract = {A new species of multicellular bacteria broadens our understanding of prokaryotic multicellularity and provides insight into how multicellular organisms arise.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Biological Evolution
RevDate: 2024-09-05
Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.
Genetics and molecular biology, 45(3):e20220065.
The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.
Additional Links: PMID-36218381
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36218381,
year = {2022},
author = {Silva, VSD and Machado, CR},
title = {Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.},
journal = {Genetics and molecular biology},
volume = {45},
number = {3},
pages = {e20220065},
pmid = {36218381},
issn = {1415-4757},
abstract = {The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.},
}
RevDate: 2022-11-14
CmpDate: 2022-10-17
What makes another life possible in bacteria? Global regulators as architects of bacterial biofilms.
World journal of microbiology & biotechnology, 38(12):236.
Biofilm structures are the main mode of evolutionary reproductive adaptation of bacteria, and even these features alone, are sufficient to make them the focus of genetic and physiological studies. As this life form is a multicellular-like life form coordinated by genetic and physiological programming, it is quite different from the planktonic form. In bacterial biofilms, which are often composed of more than one species in nature, there is a clear division of labor, nutrient channels, and a language (signaling) established between the cells forming the biofilm. On the other hand, biofilms, especially formed by pathogens, cause important industrial and clinical problems due to their high resistance to environmental stress conditions. Obtaining new data on the molecular basis of bacterial evolution and understanding the intra- and inter-species ecosystem relations in this context, as well as finding permanent solutions to the serious problems they create, are directly related to a detailed understanding of the genetic regulation of bacterial biofilm structures. Today, it is becoming increasingly certain that environmental signals effective in the transition from planktonic form to biofilm form and their receptor/response molecules are generally managed by similar systems and global regulator molecules in bacteria. In this sense; Besides the quorum sensing (QS) systems, cyclic adenosine monophosphate-catabolite suppressor protein (cAMP-CRP) and bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP) signaling molecules are of critical importance. In this review article, current information on bacterial biofilms is summarized and interpreted based on this framework.
Additional Links: PMID-36229744
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36229744,
year = {2022},
author = {Akçelik, N and Akçelik, M},
title = {What makes another life possible in bacteria? Global regulators as architects of bacterial biofilms.},
journal = {World journal of microbiology & biotechnology},
volume = {38},
number = {12},
pages = {236},
pmid = {36229744},
issn = {1573-0972},
mesh = {Adenosine Monophosphate/metabolism ; Bacteria/genetics/metabolism ; Bacterial Proteins/metabolism ; Biofilms ; Cyclic GMP/metabolism ; *Ecosystem ; *Gene Expression Regulation, Bacterial ; Guanosine Monophosphate/metabolism ; Plankton/metabolism ; Quorum Sensing/genetics ; },
abstract = {Biofilm structures are the main mode of evolutionary reproductive adaptation of bacteria, and even these features alone, are sufficient to make them the focus of genetic and physiological studies. As this life form is a multicellular-like life form coordinated by genetic and physiological programming, it is quite different from the planktonic form. In bacterial biofilms, which are often composed of more than one species in nature, there is a clear division of labor, nutrient channels, and a language (signaling) established between the cells forming the biofilm. On the other hand, biofilms, especially formed by pathogens, cause important industrial and clinical problems due to their high resistance to environmental stress conditions. Obtaining new data on the molecular basis of bacterial evolution and understanding the intra- and inter-species ecosystem relations in this context, as well as finding permanent solutions to the serious problems they create, are directly related to a detailed understanding of the genetic regulation of bacterial biofilm structures. Today, it is becoming increasingly certain that environmental signals effective in the transition from planktonic form to biofilm form and their receptor/response molecules are generally managed by similar systems and global regulator molecules in bacteria. In this sense; Besides the quorum sensing (QS) systems, cyclic adenosine monophosphate-catabolite suppressor protein (cAMP-CRP) and bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP) signaling molecules are of critical importance. In this review article, current information on bacterial biofilms is summarized and interpreted based on this framework.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Adenosine Monophosphate/metabolism
Bacteria/genetics/metabolism
Bacterial Proteins/metabolism
Biofilms
Cyclic GMP/metabolism
*Ecosystem
*Gene Expression Regulation, Bacterial
Guanosine Monophosphate/metabolism
Plankton/metabolism
Quorum Sensing/genetics
RevDate: 2022-10-19
CmpDate: 2022-10-17
Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.
International journal of molecular sciences, 23(19):.
The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.
Additional Links: PMID-36232785
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36232785,
year = {2022},
author = {Vinogradov, AE and Anatskaya, OV},
title = {Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.},
journal = {International journal of molecular sciences},
volume = {23},
number = {19},
pages = {},
pmid = {36232785},
issn = {1422-0067},
mesh = {Animals ; Biology ; Cell Differentiation/genetics ; Embryonic Stem Cells ; Humans ; *Induced Pluripotent Stem Cells ; *Neoplasms/genetics/metabolism ; Regenerative Medicine ; },
abstract = {The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Biology
Cell Differentiation/genetics
Embryonic Stem Cells
Humans
*Induced Pluripotent Stem Cells
*Neoplasms/genetics/metabolism
Regenerative Medicine
RevDate: 2022-10-19
CmpDate: 2022-10-17
The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.
Frontiers in cellular and infection microbiology, 12:985178.
Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.
Additional Links: PMID-36237424
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36237424,
year = {2022},
author = {Kumar, P and Kumar, P and Mandal, D and Velayutham, R},
title = {The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.},
journal = {Frontiers in cellular and infection microbiology},
volume = {12},
number = {},
pages = {985178},
pmid = {36237424},
issn = {2235-2988},
mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/metabolism ; Animals ; Antiparasitic Agents ; Caspases/metabolism ; *Cryptosporidiosis ; *Cryptosporidium ; Deubiquitinating Enzymes/genetics/metabolism ; Humans ; *Parasites/metabolism ; Phylogeny ; Polyubiquitin/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Ubiquitination ; },
abstract = {Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Adenosine Triphosphate/metabolism
Amino Acids/metabolism
Animals
Antiparasitic Agents
Caspases/metabolism
*Cryptosporidiosis
*Cryptosporidium
Deubiquitinating Enzymes/genetics/metabolism
Humans
*Parasites/metabolism
Phylogeny
Polyubiquitin/genetics/metabolism
Proteasome Endopeptidase Complex/metabolism
Ubiquitin/metabolism
Ubiquitination
RevDate: 2022-12-21
CmpDate: 2022-12-15
Evo-devo perspectives on cancer.
Essays in biochemistry, 66(6):797-815.
The integration of evolutionary and developmental approaches into the field of evolutionary developmental biology has opened new areas of inquiry- from understanding the evolution of development and its underlying genetic and molecular mechanisms to addressing the role of development in evolution. For the last several decades, the terms 'evolution' and 'development' have been increasingly linked to cancer, in many different frameworks and contexts. This mini-review, as part of a special issue on Evolutionary Developmental Biology, discusses the main areas in cancer research that have been addressed through the lenses of both evolutionary and developmental biology, though not always fully or explicitly integrated in an evo-devo framework. First, it briefly introduces the current views on carcinogenesis that invoke evolutionary and/or developmental perspectives. Then, it discusses the main mechanisms proposed to have specifically evolved to suppress cancer during the evolution of multicellularity. Lastly, it considers whether the evolution of multicellularity and development was shaped by the threat of cancer (a cancer-evo-devo perspective), and/or whether the evolution of developmental programs and life history traits can shape cancer resistance/risk in various lineages (an evo-devo-cancer perspective). A proper evolutionary developmental framework for cancer, both as a disease and in terms of its natural history (in the context of the evolution of multicellularity and development as well as life history traits), could bridge the currently disparate evolutionary and developmental perspectives and uncover aspects that will provide new insights for cancer prevention and treatment.
Additional Links: PMID-36250956
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36250956,
year = {2022},
author = {Nedelcu, AM},
title = {Evo-devo perspectives on cancer.},
journal = {Essays in biochemistry},
volume = {66},
number = {6},
pages = {797-815},
doi = {10.1042/EBC20220041},
pmid = {36250956},
issn = {1744-1358},
abstract = {The integration of evolutionary and developmental approaches into the field of evolutionary developmental biology has opened new areas of inquiry- from understanding the evolution of development and its underlying genetic and molecular mechanisms to addressing the role of development in evolution. For the last several decades, the terms 'evolution' and 'development' have been increasingly linked to cancer, in many different frameworks and contexts. This mini-review, as part of a special issue on Evolutionary Developmental Biology, discusses the main areas in cancer research that have been addressed through the lenses of both evolutionary and developmental biology, though not always fully or explicitly integrated in an evo-devo framework. First, it briefly introduces the current views on carcinogenesis that invoke evolutionary and/or developmental perspectives. Then, it discusses the main mechanisms proposed to have specifically evolved to suppress cancer during the evolution of multicellularity. Lastly, it considers whether the evolution of multicellularity and development was shaped by the threat of cancer (a cancer-evo-devo perspective), and/or whether the evolution of developmental programs and life history traits can shape cancer resistance/risk in various lineages (an evo-devo-cancer perspective). A proper evolutionary developmental framework for cancer, both as a disease and in terms of its natural history (in the context of the evolution of multicellularity and development as well as life history traits), could bridge the currently disparate evolutionary and developmental perspectives and uncover aspects that will provide new insights for cancer prevention and treatment.},
}
RevDate: 2023-04-18
CmpDate: 2022-10-19
Yellow polyketide pigment suppresses premature hatching in social amoeba.
Proceedings of the National Academy of Sciences of the United States of America, 119(43):e2116122119.
Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.
Additional Links: PMID-36252029
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36252029,
year = {2022},
author = {Günther, M and Reimer, C and Herbst, R and Kufs, JE and Rautschek, J and Ueberschaar, N and Zhang, S and Peschel, G and Reimer, L and Regestein, L and Valiante, V and Hillmann, F and Stallforth, P},
title = {Yellow polyketide pigment suppresses premature hatching in social amoeba.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {43},
pages = {e2116122119},
pmid = {36252029},
issn = {1091-6490},
mesh = {*Amoeba/genetics ; *Biological Products/metabolism ; *Dictyostelium/physiology ; Polyketide Synthases/genetics/metabolism ; *Polyketides/metabolism ; },
abstract = {Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Amoeba/genetics
*Biological Products/metabolism
*Dictyostelium/physiology
Polyketide Synthases/genetics/metabolism
*Polyketides/metabolism
RevDate: 2022-11-25
CmpDate: 2022-11-25
Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.
Plant molecular biology, 110(6):455-468.
Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.
Additional Links: PMID-36255595
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36255595,
year = {2022},
author = {Bano, N and Aalam, S and Bag, SK},
title = {Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.},
journal = {Plant molecular biology},
volume = {110},
number = {6},
pages = {455-468},
pmid = {36255595},
issn = {1573-5028},
mesh = {Animals ; *Transcription Factors/genetics/metabolism ; Amino Acid Sequence ; *Plants/genetics/metabolism ; Stress, Physiological ; Plant Growth Regulators/metabolism ; },
abstract = {Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Transcription Factors/genetics/metabolism
Amino Acid Sequence
*Plants/genetics/metabolism
Stress, Physiological
Plant Growth Regulators/metabolism
RevDate: 2023-10-02
CmpDate: 2022-10-24
Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.
Current protocols, 2(10):e568.
Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.
Additional Links: PMID-36264199
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36264199,
year = {2022},
author = {Whye, D and Wood, D and Kim, KH and Chen, C and Makhortova, N and Sahin, M and Buttermore, ED},
title = {Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.},
journal = {Current protocols},
volume = {2},
number = {10},
pages = {e568},
pmid = {36264199},
issn = {2691-1299},
support = {P50 HD105351/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; Pregnancy ; Female ; *Organoids ; Hedgehog Proteins ; Poloxamer ; *Pluripotent Stem Cells ; Fibroblast Growth Factors ; Retinoids ; },
abstract = {Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Pregnancy
Female
*Organoids
Hedgehog Proteins
Poloxamer
*Pluripotent Stem Cells
Fibroblast Growth Factors
Retinoids
RevDate: 2022-12-14
CmpDate: 2022-10-27
Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.
Current biology : CB, 32(20):R1028-R1029.
The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.
Additional Links: PMID-36283350
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36283350,
year = {2022},
author = {Keller, J and Delaux, PM},
title = {Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.},
journal = {Current biology : CB},
volume = {32},
number = {20},
pages = {R1028-R1029},
doi = {10.1016/j.cub.2022.09.006},
pmid = {36283350},
issn = {1879-0445},
mesh = {*Embryophyta ; Phylogeny ; Plants/genetics ; Evolution, Molecular ; Biological Evolution ; },
abstract = {The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Embryophyta
Phylogeny
Plants/genetics
Evolution, Molecular
Biological Evolution
RevDate: 2023-02-07
CmpDate: 2022-12-23
Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.
The Plant journal : for cell and molecular biology, 112(6):1507-1524.
The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.
Additional Links: PMID-36305297
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36305297,
year = {2022},
author = {León-Ruiz, JA and Cruz Ramírez, A},
title = {Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.},
journal = {The Plant journal : for cell and molecular biology},
volume = {112},
number = {6},
pages = {1507-1524},
doi = {10.1111/tpj.16012},
pmid = {36305297},
issn = {1365-313X},
mesh = {Animals ; *Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; *Retinal Neoplasms ; },
abstract = {The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Retinoblastoma
Retinoblastoma Protein/metabolism
Cell Differentiation
*Retinal Neoplasms
RevDate: 2022-11-02
Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice.
Frontiers in cellular neuroscience, 16:949412.
The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood-brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen-glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.
Additional Links: PMID-36313615
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36313615,
year = {2022},
author = {Nicolicht-Amorim, P and Delgado-Garcia, LM and Nakamura, TKE and Courbassier, NR and Mosini, AC and Porcionatto, MA},
title = {Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice.},
journal = {Frontiers in cellular neuroscience},
volume = {16},
number = {},
pages = {949412},
pmid = {36313615},
issn = {1662-5102},
abstract = {The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood-brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen-glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.},
}
RevDate: 2025-11-26
CmpDate: 2024-01-01
Viridiplantae Body Plans Viewed Through the Lens of the Fossil Record and Molecular Biology.
Integrative and comparative biology, 63(6):1316-1330.
A review of the fossil record coupled with insights gained from molecular and developmental biology reveal a series of body plan transformations that gave rise to the first land plants. Across diverse algal clades, including the green algae and their descendants, the plant body plan underwent a unicellular $\to $ colonial $\to $ simple multicellular → complex multicellular transformation series. The colonization of land involved increasing body size and associated cell specialization, including cells capable of hydraulic transport. The evolution of the life-cycle that characterizes all known land plant species involved a divergence in body plan phenotypes between the haploid and diploid generations, one adapted to facilitate sexual reproduction (a free-water dependent gametophyte) and another adapted to the dissemination of spores (a more water-independent sporophyte). The amplification of this phenotypic divergence, combined with indeterminate growth in body size, resulted in a desiccation-adapted branched sporophyte with a cuticularized epidermis, stomates, and vascular tissues. Throughout the evolution of the land plants, the body plans of the sporophyte generation involved "axiation," i.e., the acquisition of a cylindrical geometry and subsequent organographic specializations.
Additional Links: PMID-36316013
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid36316013,
year = {2023},
author = {Niklas, KJ and Tiffney, BH},
title = {Viridiplantae Body Plans Viewed Through the Lens of the Fossil Record and Molecular Biology.},
journal = {Integrative and comparative biology},
volume = {63},
number = {6},
pages = {1316-1330},
pmid = {36316013},
issn = {1557-7023},
mesh = {Animals ; *Fossils ; Plants ; *Embryophyta ; Molecular Biology ; Water ; Biological Evolution ; Phylogeny ; },
abstract = {A review of the fossil record coupled with insights gained from molecular and developmental biology reveal a series of body plan transformations that gave rise to the first land plants. Across diverse algal clades, including the green algae and their descendants, the plant body plan underwent a unicellular $\to $ colonial $\to $ simple multicellular → complex multicellular transformation series. The colonization of land involved increasing body size and associated cell specialization, including cells capable of hydraulic transport. The evolution of the life-cycle that characterizes all known land plant species involved a divergence in body plan phenotypes between the haploid and diploid generations, one adapted to facilitate sexual reproduction (a free-water dependent gametophyte) and another adapted to the dissemination of spores (a more water-independent sporophyte). The amplification of this phenotypic divergence, combined with indeterminate growth in body size, resulted in a desiccation-adapted branched sporophyte with a cuticularized epidermis, stomates, and vascular tissues. Throughout the evolution of the land plants, the body plans of the sporophyte generation involved "axiation," i.e., the acquisition of a cylindrical geometry and subsequent organographic specializations.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Fossils
Plants
*Embryophyta
Molecular Biology
Water
Biological Evolution
Phylogeny
▼ ▼ LOAD NEXT 100 CITATIONS
ESP Quick Facts
ESP Origins
In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.
ESP Support
In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.
ESP Rationale
Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.
ESP Goal
In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.
ESP Usage
Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.
ESP Content
When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.
ESP Help
Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.
ESP Plans
With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.
ESP Picks from Around the Web (updated 28 JUL 2024 )
Old Science
Weird Science
Treating Disease with Fecal Transplantation
Fossils of miniature humans (hobbits) discovered in Indonesia
Paleontology
Dinosaur tail, complete with feathers, found preserved in amber.
Astronomy
Mysterious fast radio burst (FRB) detected in the distant universe.
Big Data & Informatics
Big Data: Buzzword or Big Deal?
Hacking the genome: Identifying anonymized human subjects using publicly available data.