Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.204002
Brigitte Galliot, Yvan Wenger
The experimental and conceptual knowledge in 1909 led to the discovery of the Hydra head organizer through transplantation experiments between pigmented and non-pigmented animals; a discovery followed by numerous transplantations demonstrating cross-regulation between activating and inhibiting components distributed along the body axis. This experimental work inspired mathematicians, engineers, physicists and computer scientists to develop theoretical models predicting the principles of developmental mechanisms. Today, we know that the Wnt/β-catenin/Sp5/Zic4 gene regulatory network (GRN) links organizer activity, morphogenesis and cellular identity in Hydra, with variable conformations depending on the region or epithelial layer, and varied phenotypes depending on which GRN element is misregulated. In intact animals, Wnt/β-catenin signaling acts as the head activator at the tip of the hypostome, restricted by Sp5 in the other regions of the animal. Moreover, in the tentacle ring, Sp5 and Zic4 act epistatically to support tentacle differentiation and prevent basal disc differentiation. Along the body column, Sp5 is self-repressed in the epidermis and acts as a head inhibitor along the gastrodermis. Other players modulate these activities, such as TSP and Margin/RAX apically, Notch signaling in the tentacle zone, Dkk1/2/4 and HAS-7 in the body column. In the developmental context of regeneration, cells below the amputation zone switch from repressed to locally de novo activated head organizer status, a transition driven by immediate symmetrical and asymmetrical metabolic changes that lead to gene expression regulations involving components and modulators of Wnt/β-catenin signaling, early-pulse and early-late transient both often symmetrical, together with sustained ones, specific to head regeneration.
{"title":"Organizer formation, organizer maintenance and epithelial cell plasticity in Hydra: Role of the Wnt3/β-catenin/TCF/Sp5/Zic4 gene network","authors":"Brigitte Galliot, Yvan Wenger","doi":"10.1016/j.cdev.2025.204002","DOIUrl":"10.1016/j.cdev.2025.204002","url":null,"abstract":"<div><div>The experimental and conceptual knowledge in 1909 led to the discovery of the <em>Hydra</em> head organizer through transplantation experiments between pigmented and non-pigmented animals; a discovery followed by numerous transplantations demonstrating cross-regulation between activating and inhibiting components distributed along the body axis. This experimental work inspired mathematicians, engineers, physicists and computer scientists to develop theoretical models predicting the principles of developmental mechanisms. Today, we know that the <em>Wnt/β-catenin/Sp5/Zic4</em> gene regulatory network (GRN) links organizer activity, morphogenesis and cellular identity in <em>Hydra</em>, with variable conformations depending on the region or epithelial layer, and varied phenotypes depending on which GRN element is misregulated. In intact animals, Wnt/β-catenin signaling acts as the head activator at the tip of the hypostome, restricted by Sp5 in the other regions of the animal. Moreover, in the tentacle ring, Sp5 and Zic4 act epistatically to support tentacle differentiation and prevent basal disc differentiation. Along the body column, Sp5 is self-repressed in the epidermis and acts as a head inhibitor along the gastrodermis. Other players modulate these activities, such as TSP and Margin/RAX apically, Notch signaling in the tentacle zone, Dkk1/2/4 and HAS-7 in the body column. In the developmental context of regeneration, cells below the amputation zone switch from repressed to locally <em>de novo</em> activated head organizer status, a transition driven by immediate symmetrical and asymmetrical metabolic changes that lead to gene expression regulations involving components and modulators of Wnt/β-catenin signaling, early-pulse and early-late transient both often symmetrical, together with sustained ones, specific to head regeneration.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 204002"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2024.203972
Polina S. Timoshina , Alexey M. Nesterenko , Elena A. Parshina , Eugeny E. Orlov , Fedor M. Eroshkin , Andrey G. Zaraisky
<div><div>Embryonic scaling, the ability of embryos to regulate their spatial structure in proportion to size, remains a fascinating yet poorly studied problem in developmental biology. First described in sea urchin embryos by Hans Driesch, this phenomenon is now recognized as a striking example of how living organisms use non-equilibrium self-organization, based on reaction-diffusion (RD) systems, to generate pattern-determining morphogen concentration gradients that scale with size. Although specific molecular mechanisms for scaling such gradients have been described in some cases, a general approach for the targeted identification of such mechanisms had not been developed until recently. In search of a solution, we hypothesized the obligatory participation in scaling mechanisms of special genes, which we named “<em>scalers.</em>” We supposed that these genes share two critical features: their expression is sensitive to embryo size, and their protein products determine the scale of morphogen concentration gradients. As proof of principle, we recently identified <em>scalers</em> by detecting differentially expressed genes in wild-type and half-size <em>Xenopus laevis</em> gastrula embryos. Furthermore, we described a mechanism by which one of the identified <em>scalers</em>, the gene encoding Metalloproteinase 3 (Mmp3), regulates the scaling of gradients of the morphogenic protein Bmp and its antagonists, Chordin and Noggin1/2. In the present work, we have made an important theoretical generalization of the <em>Scalers</em> Hypothesis by proving a statement regarding the obligatory presence of <em>scalers</em> in closed RD systems generating morphogen concentration gradients. Furthermore, through a systematic analysis of all known types of embryonic scaling models based on RD systems, we demonstrate that <em>scalers</em> are present in all known types of such models, either explicitly or implicitly. Finally, to test the universality of the <em>Scalers</em> Hypothesis, we applied our method to identify scalers that adjust Bmp/Chordin gradients to the size of the sea urchin embryo, <em>Strongylocentrotus droebachiensis</em>. Our results show that at least two members of the gene cluster encoding astacin metalloproteinases of the Span family, namely bp10 and Span, exhibit properties characteristic of <em>scalers</em>. Namely, their expression levels increase significantly in half-size embryos, and their protein products specifically degrade Chordin. Additionally, we found that the loss of function of <em>bp10</em> and <em>span</em> leads to a narrowing of the dorsal domain of the Bmp signaling nuclear effector, pSmad1/5. These findings not only validate the <em>Scalers</em> Hypothesis but also uncover a novel mechanism by which Span proteinases fine-tune Chordin and Bmp morphogen concentration gradients in sea urchins. Thus, the <em>Scalers</em> Hypothesis and the approach to targeted search for such genes developed on its basis open up promising a
{"title":"Dissecting the mystery of embryonic scaling: The Scalers Hypothesis and its confirmation in sea urchin embryos","authors":"Polina S. Timoshina , Alexey M. Nesterenko , Elena A. Parshina , Eugeny E. Orlov , Fedor M. Eroshkin , Andrey G. Zaraisky","doi":"10.1016/j.cdev.2024.203972","DOIUrl":"10.1016/j.cdev.2024.203972","url":null,"abstract":"<div><div>Embryonic scaling, the ability of embryos to regulate their spatial structure in proportion to size, remains a fascinating yet poorly studied problem in developmental biology. First described in sea urchin embryos by Hans Driesch, this phenomenon is now recognized as a striking example of how living organisms use non-equilibrium self-organization, based on reaction-diffusion (RD) systems, to generate pattern-determining morphogen concentration gradients that scale with size. Although specific molecular mechanisms for scaling such gradients have been described in some cases, a general approach for the targeted identification of such mechanisms had not been developed until recently. In search of a solution, we hypothesized the obligatory participation in scaling mechanisms of special genes, which we named “<em>scalers.</em>” We supposed that these genes share two critical features: their expression is sensitive to embryo size, and their protein products determine the scale of morphogen concentration gradients. As proof of principle, we recently identified <em>scalers</em> by detecting differentially expressed genes in wild-type and half-size <em>Xenopus laevis</em> gastrula embryos. Furthermore, we described a mechanism by which one of the identified <em>scalers</em>, the gene encoding Metalloproteinase 3 (Mmp3), regulates the scaling of gradients of the morphogenic protein Bmp and its antagonists, Chordin and Noggin1/2. In the present work, we have made an important theoretical generalization of the <em>Scalers</em> Hypothesis by proving a statement regarding the obligatory presence of <em>scalers</em> in closed RD systems generating morphogen concentration gradients. Furthermore, through a systematic analysis of all known types of embryonic scaling models based on RD systems, we demonstrate that <em>scalers</em> are present in all known types of such models, either explicitly or implicitly. Finally, to test the universality of the <em>Scalers</em> Hypothesis, we applied our method to identify scalers that adjust Bmp/Chordin gradients to the size of the sea urchin embryo, <em>Strongylocentrotus droebachiensis</em>. Our results show that at least two members of the gene cluster encoding astacin metalloproteinases of the Span family, namely bp10 and Span, exhibit properties characteristic of <em>scalers</em>. Namely, their expression levels increase significantly in half-size embryos, and their protein products specifically degrade Chordin. Additionally, we found that the loss of function of <em>bp10</em> and <em>span</em> leads to a narrowing of the dorsal domain of the Bmp signaling nuclear effector, pSmad1/5. These findings not only validate the <em>Scalers</em> Hypothesis but also uncover a novel mechanism by which Span proteinases fine-tune Chordin and Bmp morphogen concentration gradients in sea urchins. Thus, the <em>Scalers</em> Hypothesis and the approach to targeted search for such genes developed on its basis open up promising a","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203972"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.204000
Jan Stundl, Marianne E. Bronner
Neural crest induction begins at the neural plate border and involves the intricate interplay of signaling and transcriptional events. In this review, we examine the literature on neural crest induction, focusing primarily on the chick model due to the extended time during which the induction process occurs. While it is well-established that induction initiates during mid-gastrulation, evidence from tissue recombination and transcriptomic analyses suggests that the process continues until neural tube closure. Along the body axis, distinct neural crest populations with varying developmental potentials emerge in a rostral to caudal progression. Testing axial level differences has revealed axial level specific subcircuits that influence region-specific neural crest cell fate decision, though what leads to axial level specification remains unknown.
{"title":"Tempting fate: Neural crest induction along the body axis","authors":"Jan Stundl, Marianne E. Bronner","doi":"10.1016/j.cdev.2025.204000","DOIUrl":"10.1016/j.cdev.2025.204000","url":null,"abstract":"<div><div>Neural crest induction begins at the neural plate border and involves the intricate interplay of signaling and transcriptional events. In this review, we examine the literature on neural crest induction, focusing primarily on the chick model due to the extended time during which the induction process occurs. While it is well-established that induction initiates during mid-gastrulation, evidence from tissue recombination and transcriptomic analyses suggests that the process continues until neural tube closure. Along the body axis, distinct neural crest populations with varying developmental potentials emerge in a rostral to caudal progression. Testing axial level differences has revealed axial level specific subcircuits that influence region-specific neural crest cell fate decision, though what leads to axial level specification remains unknown.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 204000"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.203998
L.E. Sánchez-Cisneros , M.F. Frutis-Osorio , L.D. Ríos-Barrera
Throughout embryonic development, cells respond to a diverse set of signals and forces, making individual or collective decisions that drive the formation of specialized tissues. The development of these structures is tightly regulated in space and time. In recent years, the possibility that neighboring tissues influence one another's morphogenesis has been explored, as some of them develop simultaneously. We study this issue by reviewing the interactions between Drosophila epidermal and tracheal tissues in early and late stages of embryogenesis. Early in development, the epidermis emerges from the ectodermal layer. During its differentiation, epidermal cells produce morphogen gradients that influence the fundamental organization of the embryo. In this work, we analyze how molecules produced by the epidermis guide tracheal system development. Since both tissues emerge from the same germ layer and lie in close proximity all along their development, they are an excellent model for studying induction processes and tissue interactions.
{"title":"A tale of two tissues: Patterning of the epidermis through morphogens and their role in establishing tracheal system organization","authors":"L.E. Sánchez-Cisneros , M.F. Frutis-Osorio , L.D. Ríos-Barrera","doi":"10.1016/j.cdev.2025.203998","DOIUrl":"10.1016/j.cdev.2025.203998","url":null,"abstract":"<div><div>Throughout embryonic development, cells respond to a diverse set of signals and forces, making individual or collective decisions that drive the formation of specialized tissues. The development of these structures is tightly regulated in space and time. In recent years, the possibility that neighboring tissues influence one another's morphogenesis has been explored, as some of them develop simultaneously. We study this issue by reviewing the interactions between <em>Drosophila</em> epidermal and tracheal tissues in early and late stages of embryogenesis. Early in development, the epidermis emerges from the ectodermal layer. During its differentiation, epidermal cells produce morphogen gradients that influence the fundamental organization of the embryo. In this work, we analyze how molecules produced by the epidermis guide tracheal system development. Since both tissues emerge from the same germ layer and lie in close proximity all along their development, they are an excellent model for studying induction processes and tissue interactions.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203998"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/S2667-2901(25)00077-4
{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S2667-2901(25)00077-4","DOIUrl":"10.1016/S2667-2901(25)00077-4","url":null,"abstract":"","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 204070"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.cdev.2025.204043
Ulla-Maj Fiuza , Sara Bonavia , Pau Pascual-Mas , Gabriel Torregrosa-Cortés , Pablo Casaní-Galdón , Gaëlle Robertson , André Dias , Alfonso Martinez Arias
Mammalian embryonic size is tightly controlled with checkpoints and compensatory mechanisms correcting size defects. Here, we take advantage of gastruloids, a stem cell embryoid system not subject to most size controls, to study the role of size in emergent properties of mammalian embryogenesis. We report that gastruloids exhibit robust morphology and transcriptional profiles within a size range. However, size affects the dynamics, and, outside a range of robust morphogenesis, the precision of anterior-posterior (AP) axial elongation. Gastruloid axial elongation exhibits active cellular contractility, requires planar cell polarity (PCP), adhesion and cell-cell contact remodelling. Smaller gastruloids initiate elongation earlier, correlated with an earlier Brachyury polarisation. Brachyury expression increases tissue fluidity. Axis formation is regulated by the balance of Brachyury multifoci coalescence and the timing of initiation of the elongation programme. Sizes beyond the robust range can modify relative tissue composition. Very small aggregates have increased neural fate bias, accompanied by a loss of paraxial mesoderm mediated by differences in Nodal signalling activity.
{"title":"Morphogenetic constraints in the development of gastruloids: Implications for mouse gastrulation","authors":"Ulla-Maj Fiuza , Sara Bonavia , Pau Pascual-Mas , Gabriel Torregrosa-Cortés , Pablo Casaní-Galdón , Gaëlle Robertson , André Dias , Alfonso Martinez Arias","doi":"10.1016/j.cdev.2025.204043","DOIUrl":"10.1016/j.cdev.2025.204043","url":null,"abstract":"<div><div>Mammalian embryonic size is tightly controlled with checkpoints and compensatory mechanisms correcting size defects. Here, we take advantage of gastruloids, a stem cell embryoid system not subject to most size controls, to study the role of size in emergent properties of mammalian embryogenesis. We report that gastruloids exhibit robust morphology and transcriptional profiles within a size range. However, size affects the dynamics, and, outside a range of robust morphogenesis, the precision of anterior-posterior (AP) axial elongation. Gastruloid axial elongation exhibits active cellular contractility, requires planar cell polarity (PCP), adhesion and cell-cell contact remodelling. Smaller gastruloids initiate elongation earlier, correlated with an earlier Brachyury polarisation. Brachyury expression increases tissue fluidity. Axis formation is regulated by the balance of Brachyury multifoci coalescence and the timing of initiation of the elongation programme. Sizes beyond the robust range can modify relative tissue composition. Very small aggregates have increased neural fate bias, accompanied by a loss of paraxial mesoderm mediated by differences in Nodal signalling activity.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"183 ","pages":"Article 204043"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.cdev.2025.204041
Wen Jun Thang
A rapid construction of vasculature ensures the survival and proper functions of tissue-engineered constructs for oral and craniofacial tissue regeneration. Vascularization achieved via a co-culture system containing endothelial cells (ECs) and other supporting cells is more advantageous compared to host angiogenic ingrowth, as it allows faster vessel formation or even prevascularization. Among different sources of ECs, the multidifferentiation capacity of oral cavity-derived mesenchymal stem/stromal cells (MSCs) indicates their potential to give rise to autologous ECs for use in vascular tissue engineering. Considering the growing interest in vascularization in tissue engineering, this review intends to provide a comprehensive overview of the endothelial differentiation of human oral cavity-derived MSCs. Specifically, the author begins by scrutinizing the scientific justification and biological feasibility of employing MSC-derived ECs, followed by an exploration of the criteria and assessment of both in vitro and in vivo endothelial differentiation and a compilation of different strategies for endothelial differentiation induction and their underlying mechanisms. Subsequently, the different aspects pertinent to the practical considerations, including the characteristics and optimization of endothelial differentiation protocols/strategies, culture conditions, and cell origin and subpopulations, are also discussed to guide the selection of the differentiation approach and to understand the factors affecting the differentiation outcome. Finally, the present technical, biological, and clinical constraints and future perspectives are also provided. Gaining a comprehensive knowledge of these topics may provide a cornerstone for the potential derivation of functional and mature ECs from oral cavity-derived MSCs, which will certainly provide clinical value for oral and craniofacial tissue regeneration.
{"title":"Endothelial differentiation of Oral cavity-derived mesenchymal stem/stromal cells","authors":"Wen Jun Thang","doi":"10.1016/j.cdev.2025.204041","DOIUrl":"10.1016/j.cdev.2025.204041","url":null,"abstract":"<div><div>A rapid construction of vasculature ensures the survival and proper functions of tissue-engineered constructs for oral and craniofacial tissue regeneration. Vascularization achieved via a co-culture system containing endothelial cells (ECs) and other supporting cells is more advantageous compared to host angiogenic ingrowth, as it allows faster vessel formation or even prevascularization. Among different sources of ECs, the multidifferentiation capacity of oral cavity-derived mesenchymal stem/stromal cells (MSCs) indicates their potential to give rise to autologous ECs for use in vascular tissue engineering. Considering the growing interest in vascularization in tissue engineering, this review intends to provide a comprehensive overview of the endothelial differentiation of human oral cavity-derived MSCs. Specifically, the author begins by scrutinizing the scientific justification and biological feasibility of employing MSC-derived ECs, followed by an exploration of the criteria and assessment of both in vitro and in vivo endothelial differentiation and a compilation of different strategies for endothelial differentiation induction and their underlying mechanisms. Subsequently, the different aspects pertinent to the practical considerations, including the characteristics and optimization of endothelial differentiation protocols/strategies, culture conditions, and cell origin and subpopulations, are also discussed to guide the selection of the differentiation approach and to understand the factors affecting the differentiation outcome. Finally, the present technical, biological, and clinical constraints and future perspectives are also provided. Gaining a comprehensive knowledge of these topics may provide a cornerstone for the potential derivation of functional and mature ECs from oral cavity-derived MSCs, which will certainly provide clinical value for oral and craniofacial tissue regeneration.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"183 ","pages":"Article 204041"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/S2667-2901(25)00057-9
{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S2667-2901(25)00057-9","DOIUrl":"10.1016/S2667-2901(25)00057-9","url":null,"abstract":"","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"183 ","pages":"Article 204050"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.cdev.2025.204039
Yeo Gyun Yun , Donghyeon Yeo , Trang Thanh Thien Tran , Seong-Jin Shin , Ji-Sun Shin , Nam Kyu Lim , Jun Hee Lee , Hae-Won Kim
Under physiological conditions, adult stem cells are located in a special microenvironment, known as the niche, which is characterized by low oxygen levels. Hypoxia is a crucial factor regulating stem cell behavior, and in vitro normoxic culture often leads to the loss of pluripotency, resulting in reduced therapeutic potential of cells. In this study, we aimed to investigate the effects of cobalt chloride (CoCl2), a hypoxia-mimetic agent, on mesenchymal stem cells (MSCs) derived from different sources by inducing hypoxia-inducible factor-1α. Cell proliferation, migration, survival, and metabolic activity were assessed. CoCl2 treatment decreased the proliferation and migration and enhanced the survival of MSCs. Furthermore, a metabolic shift from oxidative phosphorylation to glycolysis was observed in cells. Overall, our findings provide important insights into the mechanisms by which hypoxic conditions differentially influence stem cells, facilitating the improvement of their therapeutic potential.
{"title":"The characterization of the biological effect of hypoxia-mimetic condition on angiogenic potential in mesenchymal stem cells derived from different origins","authors":"Yeo Gyun Yun , Donghyeon Yeo , Trang Thanh Thien Tran , Seong-Jin Shin , Ji-Sun Shin , Nam Kyu Lim , Jun Hee Lee , Hae-Won Kim","doi":"10.1016/j.cdev.2025.204039","DOIUrl":"10.1016/j.cdev.2025.204039","url":null,"abstract":"<div><div>Under physiological conditions, adult stem cells are located in a special microenvironment, known as the niche, which is characterized by low oxygen levels. Hypoxia is a crucial factor regulating stem cell behavior, and in vitro normoxic culture often leads to the loss of pluripotency, resulting in reduced therapeutic potential of cells. In this study, we aimed to investigate the effects of cobalt chloride (CoCl<sub>2</sub>), a hypoxia-mimetic agent, on mesenchymal stem cells (MSCs) derived from different sources by inducing hypoxia-inducible factor-1α. Cell proliferation, migration, survival, and metabolic activity were assessed. CoCl<sub>2</sub> treatment decreased the proliferation and migration and enhanced the survival of MSCs. Furthermore, a metabolic shift from oxidative phosphorylation to glycolysis was observed in cells. Overall, our findings provide important insights into the mechanisms by which hypoxic conditions differentially influence stem cells, facilitating the improvement of their therapeutic potential.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"183 ","pages":"Article 204039"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1016/j.cdev.2025.204040
Seyhmus Bayar , Lea Seep , Karolína Doubková , Jelena Zurkovic , Margret H. Bülow , Katrin Kierdorf , Reinhard Bauer , Christoph Thiele , Gaia Tavosanis , Jan Hasenauer , Elvira Mass
Maternal obesity is a growing health concern that predisposes offspring to metabolic dysfunction, immune system alterations, and neurodegenerative disorders. To investigate the intergenerational effects of maternal obesity, we used Drosophila melanogaster exposed to high-sugar (HSD) and high-fat diets (HFD) before mating. We found that maternal diet-induced obesity significantly altered offspring lifespan, immune responses, and neuronal health in a sex- and diet-specific manner. Male offspring were particularly susceptible, exhibiting reduced lifespan, impaired climbing ability, and increased axonal degeneration, especially following maternal HFD exposure. Transcriptomic analyses revealed age-dependent and diet-specific changes, with males showing pronounced alterations at 50 days of age. Developmental programming of hemocytes (blood-like cells) played a crucial role in these outcomes, as knockdown of key immune pathways such as Relish and upd3 in hemocytes further influenced lifespan in a diet-specific manner. These findings highlight the complex interplay between maternal diet and immune function, underscoring the impact of maternal obesity-induced imprinting on immune cells and subsequent long-term health consequences. Our study provides new insights into conserved mechanisms linking maternal metabolic health to offspring outcomes and emphasizes the continued need for animal models to understand intergenerational health impacts.
{"title":"Developmental programming by maternal obesity alters offspring lifespan and immune responses in a diet- and sex-specific manner","authors":"Seyhmus Bayar , Lea Seep , Karolína Doubková , Jelena Zurkovic , Margret H. Bülow , Katrin Kierdorf , Reinhard Bauer , Christoph Thiele , Gaia Tavosanis , Jan Hasenauer , Elvira Mass","doi":"10.1016/j.cdev.2025.204040","DOIUrl":"10.1016/j.cdev.2025.204040","url":null,"abstract":"<div><div>Maternal obesity is a growing health concern that predisposes offspring to metabolic dysfunction, immune system alterations, and neurodegenerative disorders. To investigate the intergenerational effects of maternal obesity, we used <em>Drosophila melanogaster</em> exposed to high-sugar (HSD) and high-fat diets (HFD) before mating. We found that maternal diet-induced obesity significantly altered offspring lifespan, immune responses, and neuronal health in a sex- and diet-specific manner. Male offspring were particularly susceptible, exhibiting reduced lifespan, impaired climbing ability, and increased axonal degeneration, especially following maternal HFD exposure. Transcriptomic analyses revealed age-dependent and diet-specific changes, with males showing pronounced alterations at 50 days of age. Developmental programming of hemocytes (blood-like cells) played a crucial role in these outcomes, as knockdown of key immune pathways such as <em>Relish</em> and <em>upd3</em> in hemocytes further influenced lifespan in a diet-specific manner. These findings highlight the complex interplay between maternal diet and immune function, underscoring the impact of maternal obesity-induced imprinting on immune cells and subsequent long-term health consequences. Our study provides new insights into conserved mechanisms linking maternal metabolic health to offspring outcomes and emphasizes the continued need for animal models to understand intergenerational health impacts.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"183 ","pages":"Article 204040"},"PeriodicalIF":3.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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