{"title":"Efficient generation of human immune system rats using human CD34<sup>+</sup> cells.","authors":"Séverine Ménoret, Florence Renart-Depontieu, Gaelle Martin, Kader Thiam, Ignacio Anegon","doi":"10.1016/j.stemcr.2024.07.005","DOIUrl":"10.1016/j.stemcr.2024.07.005","url":null,"abstract":"<p><p>Human immune system (HIS) mice generated using human CD34<sup>+</sup> hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments. Here, we describe an efficacious method for long-term immune humanization, through intrahepatic injection of hCD34<sup>+</sup> cells in newborn immunodeficient rats expressing human SIRPα. In contrast to HIS mice and similar to humans, HIS rats showed in blood a predominance of T cells, followed by B cells. Immune humanization was also high in central and secondary lymphoid organs. HIS rats treated with the anti-human CD3 antibody were depleted of human T cells, and human cytokines were detected in sera. We describe for the first time a method to efficiently generate HIS rats. HIS rats have the potential to be a useful model for translational immunology.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1255-1263"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-22DOI: 10.1016/j.stemcr.2024.07.009
Rebecca Gorelov, Aaron Weiner, Aaron Huebner, Masaki Yagi, Amin Haghani, Robert Brooke, Steve Horvath, Konrad Hochedlinger
{"title":"Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks.","authors":"Rebecca Gorelov, Aaron Weiner, Aaron Huebner, Masaki Yagi, Amin Haghani, Robert Brooke, Steve Horvath, Konrad Hochedlinger","doi":"10.1016/j.stemcr.2024.07.009","DOIUrl":"10.1016/j.stemcr.2024.07.009","url":null,"abstract":"<p><p>Epigenetic clocks, built on DNA methylation patterns of bulk tissues, are powerful age predictors, but their biological basis remains incompletely understood. Here, we conducted a comparative analysis of epigenetic age in murine muscle, epithelial, and blood cell types across lifespan. Strikingly, our results show that cellular subpopulations within these tissues, including adult stem and progenitor cells as well as their differentiated progeny, exhibit different epigenetic ages. Accordingly, we experimentally demonstrate that clocks can be skewed by age-associated changes in tissue composition. Mechanistically, we provide evidence that the observed variation in epigenetic age among adult stem cells correlates with their proliferative state, and, fittingly, forced proliferation of stem cells leads to increases in epigenetic age. Collectively, our analyses elucidate the impact of cell type composition, differentiation state, and replicative potential on epigenetic age, which has implications for the interpretation of existing clocks and should inform the development of more sensitive clocks.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1242-1254"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-22DOI: 10.1016/j.stemcr.2024.07.008
Madison R Glass, Elisa A Waxman, Satoshi Yamashita, Michael Lafferty, Alvaro A Beltran, Tala Farah, Niyanta K Patel, Rubal Singla, Nana Matoba, Sara Ahmed, Mary Srivastava, Emma Drake, Liam T Davis, Meghana Yeturi, Kexin Sun, Michael I Love, Kazue Hashimoto-Torii, Deborah L French, Jason L Stein
{"title":"Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture.","authors":"Madison R Glass, Elisa A Waxman, Satoshi Yamashita, Michael Lafferty, Alvaro A Beltran, Tala Farah, Niyanta K Patel, Rubal Singla, Nana Matoba, Sara Ahmed, Mary Srivastava, Emma Drake, Liam T Davis, Meghana Yeturi, Kexin Sun, Michael I Love, Kazue Hashimoto-Torii, Deborah L French, Jason L Stein","doi":"10.1016/j.stemcr.2024.07.008","DOIUrl":"10.1016/j.stemcr.2024.07.008","url":null,"abstract":"<p><p>While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types at one site, variability in hCO phenotypes across sites using a harmonized protocol has not yet been evaluated. To determine the cross-site reproducibility of hCO differentiation, three independent research groups assayed hCOs in multiple differentiation replicates from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol across 3 months. hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and expression of metabolism and cellular stress genes. Variability in hCO phenotypes correlated with stem cell gene expression prior to differentiation and technical factors associated with seeding, suggesting iPSC quality and treatment are important for differentiation outcomes. Cross-site reproducibility of hCO cell type proportions and organization encourages future prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1351-1367"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-15DOI: 10.1016/j.stemcr.2024.07.004
Suel-Kee Kim, Seungmae Seo, Genevieve Stein-O'Brien, Amritha Jaishankar, Kazuya Ogawa, Nicola Micali, Victor Luria, Amir Karger, Yanhong Wang, Hyojin Kim, Thomas M Hyde, Joel E Kleinman, Ty Voss, Elana J Fertig, Joo-Heon Shin, Roland Bürli, Alan J Cross, Nicholas J Brandon, Daniel R Weinberger, Joshua G Chenoweth, Daniel J Hoeppner, Nenad Sestan, Carlo Colantuoni, Ronald D McKay
{"title":"Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.","authors":"Suel-Kee Kim, Seungmae Seo, Genevieve Stein-O'Brien, Amritha Jaishankar, Kazuya Ogawa, Nicola Micali, Victor Luria, Amir Karger, Yanhong Wang, Hyojin Kim, Thomas M Hyde, Joel E Kleinman, Ty Voss, Elana J Fertig, Joo-Heon Shin, Roland Bürli, Alan J Cross, Nicholas J Brandon, Daniel R Weinberger, Joshua G Chenoweth, Daniel J Hoeppner, Nenad Sestan, Carlo Colantuoni, Ronald D McKay","doi":"10.1016/j.stemcr.2024.07.004","DOIUrl":"10.1016/j.stemcr.2024.07.004","url":null,"abstract":"<p><p>Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1336-1350"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-29DOI: 10.1016/j.stemcr.2024.08.001
Madison B Wilken, Gennadiy Fonar, Rong Qiu, Laura Bennett, Joanna Tober, Catriana Nations, Giulia Pavani, Victor Tsao, James Garifallou, Chayanne Petit, Jean Ann Maguire, Alyssa Gagne, Nkemdilim Okoli, Paul Gadue, Stella T Chou, Deborah L French, Nancy A Speck, Christopher S Thom
{"title":"Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis.","authors":"Madison B Wilken, Gennadiy Fonar, Rong Qiu, Laura Bennett, Joanna Tober, Catriana Nations, Giulia Pavani, Victor Tsao, James Garifallou, Chayanne Petit, Jean Ann Maguire, Alyssa Gagne, Nkemdilim Okoli, Paul Gadue, Stella T Chou, Deborah L French, Nancy A Speck, Christopher S Thom","doi":"10.1016/j.stemcr.2024.08.001","DOIUrl":"10.1016/j.stemcr.2024.08.001","url":null,"abstract":"<p><p>Tropomyosins coat actin filaments to impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. TPM1 has been shown to regulate blood cell formation in vitro, but it remains unclear how or when TPM1 affects hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, we found that TPM1 knockout augmented developmental cell state transitions and key signaling pathways, including tumor necrosis factor alpha (TNF-α) signaling, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses revealed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced HE formation during embryogenesis, without increasing the number of hematopoietic stem cells. These findings illuminate novel effects of TPM1 on developmental hematopoiesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1264-1276"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-22DOI: 10.1016/j.stemcr.2024.07.010
Ioannis Oikonomakos, Melina Tedesco, Fariba Jian Motamedi, Mirko Peitzsch, Serge Nef, Stefan R Bornstein, Andreas Schedl, Charlotte Steenblock, Yasmine Neirijnck
{"title":"In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells.","authors":"Ioannis Oikonomakos, Melina Tedesco, Fariba Jian Motamedi, Mirko Peitzsch, Serge Nef, Stefan R Bornstein, Andreas Schedl, Charlotte Steenblock, Yasmine Neirijnck","doi":"10.1016/j.stemcr.2024.07.010","DOIUrl":"10.1016/j.stemcr.2024.07.010","url":null,"abstract":"<p><p>Directed differentiation of pluripotent stem cells into specialized cell types represents an invaluable tool for a wide range of applications. Here, we have exploited single-cell transcriptomic data to develop a stepwise in vitro differentiation system from mouse embryonic stem cells into adrenocortical cells. We show that during development, the adrenal primordium is embedded in an extracellular matrix containing tenascin and fibronectin. Culturing cells on fibronectin during differentiation increased the expression of the steroidogenic marker NR5A1. Furthermore, 3D cultures in the presence of protein kinase A (PKA)-pathway activators led to the formation of aggregates composed of different cell types expressing adrenal progenitor or steroidogenic markers, including the adrenocortical-specific enzyme CYP21A1. Importantly, in-vitro-differentiated cells responded to adrenocorticotropic hormone (ACTH) and angiotensin II with the production of glucocorticoids and mineralocorticoids, respectively, thus confirming the specificity of differentiation toward the adrenal lineage.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1289-1303"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells.","authors":"Chengcheng Song, Zhaoying Zhang, Dongliang Leng, Ziqing He, Xuepeng Wang, Weiwei Liu, Wensheng Zhang, Qiang Wu, Qi Zhao, Guokai Chen","doi":"10.1016/j.stemcr.2024.07.007","DOIUrl":"10.1016/j.stemcr.2024.07.007","url":null,"abstract":"<p><p>The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor β (TGF-β), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-β. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1320-1335"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-09-10Epub Date: 2024-08-15DOI: 10.1016/j.stemcr.2024.07.006
Rosario Isasi, Heidi B Bentzen, Morris Fabbri, Antonie Fuhr, Joel C Glover, Nancy Mah, Deborah Mascalzoni, Sabine Mueller, Stefanie Seltmann, Andreas Kurtz
{"title":"Dynamic governance: A new era for consent for stem cell research.","authors":"Rosario Isasi, Heidi B Bentzen, Morris Fabbri, Antonie Fuhr, Joel C Glover, Nancy Mah, Deborah Mascalzoni, Sabine Mueller, Stefanie Seltmann, Andreas Kurtz","doi":"10.1016/j.stemcr.2024.07.006","DOIUrl":"10.1016/j.stemcr.2024.07.006","url":null,"abstract":"<p><p>Governance infrastructures streamline scientific and ethical provenance verification of human pluripotent stem cell (SC) lines. Yet, scientific developments (e.g., SC-derived embryo models, organoids) challenge research governance approaches to stored biospecimens, questioning the validity of informed consent (IC) models. Likewise, e-health platforms are driving major transformations in data processing, prompting a reappraisal of IC. Given these developments, participatory research platforms are identified as effective tools to promote longitudinal engagement, interactive decision-making, and dynamic governance. Learning from European initiatives piloting dynamic IC for biobanking and SC research, this Perspective explores the benefits and challenges of implementing dynamic IC and governance for SC.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1233-1241"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-08-13Epub Date: 2024-08-01DOI: 10.1016/j.stemcr.2024.07.002
Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer
{"title":"Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.","authors":"Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer","doi":"10.1016/j.stemcr.2024.07.002","DOIUrl":"10.1016/j.stemcr.2024.07.002","url":null,"abstract":"<p><p>Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1122-1136"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell size regulates human endoderm specification through actomyosin-dependent AMOT-YAP signaling.","authors":"Lai Jiang, Chenchao Yan, Ying Yi, Lihang Zhu, Zheng Liu, Donghui Zhang, Wei Jiang","doi":"10.1016/j.stemcr.2024.07.001","DOIUrl":"10.1016/j.stemcr.2024.07.001","url":null,"abstract":"<p><p>Cell size is a crucial physical property that significantly impacts cellular physiology and function. However, the influence of cell size on stem cell specification remains largely unknown. Here, we investigated the dynamic changes in cell size during the differentiation of human pluripotent stem cells into definitive endoderm (DE). Interestingly, cell size exhibited a gradual decrease as DE differentiation progressed with higher stiffness. Furthermore, the application of hypertonic pressure or chemical to accelerate the reduction in cell size significantly and specifically enhanced DE differentiation. By functionally intervening in mechanosensitive elements, we have identified actomyosin activity as a crucial mediator of both DE differentiation and cell size reduction. Mechanistically, the reduction in cell size induces actomyosin-dependent angiomotin (AMOT) nuclear translocation, which suppresses Yes-associated protein (YAP) activity and thus facilitates DE differentiation. Together, our study has established a novel connection between cell size diminution and DE differentiation, which is mediated by AMOT nuclear translocation. Additionally, our findings suggest that the application of osmotic pressure can effectively promote human endodermal lineage differentiation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1137-1155"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
