Stem Cell Reports最新文献_第4页

In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells. 将小鼠多能干细胞体外分化为产生皮质类固醇的肾上腺皮质细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI: 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":"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.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"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}

引用次数: 0

ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells. ERK5促进自分泌表达，以维持人类多能干细胞中细胞命运规范的有丝分裂平衡。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI: 10.1016/j.stemcr.2024.07.007

Chengcheng Song, Zhaoying Zhang, Dongliang Leng, Ziqing He, Xuepeng Wang, Weiwei Liu, Wensheng Zhang, Qiang Wu, Qi Zhao, Guokai Chen

{"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":"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.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"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}

引用次数: 0

Dynamic governance: A new era for consent for stem cell research. 动态管理：干细胞研究同意的新时代。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI: 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

引用次数: 0

Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models. 在人类多能干细胞模型中，诱导星形胶质细胞反应性会促进神经退行性变。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI: 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":"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.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"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}

引用次数: 0

Cell size regulates human endoderm specification through actomyosin-dependent AMOT-YAP signaling. 细胞大小通过肌动蛋白依赖性AMOT-YAP信号传导调节人类内胚层的规格。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI: 10.1016/j.stemcr.2024.07.001

Lai Jiang, Chenchao Yan, Ying Yi, Lihang Zhu, Zheng Liu, Donghui Zhang, Wei Jiang

{"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":"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.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"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}

引用次数: 0

Ras promotes germline stem cell division in Drosophila ovaries. Ras 促进果蝇卵巢生殖干细胞分裂

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-18 DOI: 10.1016/j.stemcr.2024.06.005

Qi Zhang, Yanfang Wang, Zhenan Bu, Yang Zhang, Qian Zhang, Le Li, Lizhong Yan, Yuejia Wang, Shaowei Zhao

{"title":"Ras promotes germline stem cell division in Drosophila ovaries.","authors":"Qi Zhang, Yanfang Wang, Zhenan Bu, Yang Zhang, Qian Zhang, Le Li, Lizhong Yan, Yuejia Wang, Shaowei Zhao","doi":"10.1016/j.stemcr.2024.06.005","DOIUrl":"10.1016/j.stemcr.2024.06.005","url":null,"abstract":"The Ras family genes are proto-oncogenes that are highly conserved from Drosophila to humans. In Drosophila, RasV12 is a constitutively activated form of the Ras oncoprotein, and its function in cell-cycle progression is context dependent. However, how it influences the cell cycle of female germline stem cells (GSCs) still remains unknown. Using both wild-type GSCs and bam mutant GSC-like cells as model systems, here we determined that RasV12 overexpression promotes GSC division, not growth, opposite to that in somatic wing disc cells. Ras performs this function through activating the mitogen-activated protein kinase (MAPK) signaling. This signaling is activated specifically in the M phase of mitotic germ cells, including both wild-type GSCs and bam mutant GSC-like cells. Furthermore, RasV12 overexpression triggers polyploid nurse cells to die through inducing mitotic stress. Given the similarities between Drosophila and mammalian GSCs, we propose that the Ras/MAPK signaling also promotes mammalian GSC division.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727880","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}

引用次数: 0

The impact of consanguinity on the design of iPSC banks. 近亲结婚对 iPSC 库设计的影响。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-11 DOI: 10.1016/j.stemcr.2024.06.004

Imen F Alkuraya, Edward B De Vol

引用次数: 0

Advanced human embryo research beyond the 14-day limit: A bioethical perspective from the Muslim world. 超过 14 天限制的先进人类胚胎研究：穆斯林世界的生物伦理视角。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.008

Mohammed Ghaly, Essam M Abdelalim

引用次数: 0

Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart. 移植的多能干细胞衍生心肌细胞的脉冲启动可刺激受体心脏。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.012

Tim Stüdemann, Barbora Schwarzová, Till Schneidewind, Birgit Geertz, Constantin von Bibra, Marie Nehring, Judith Rössinger, J Simon Wiegert, Thomas Eschenhagen, Florian Weinberger

{"title":"Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart.","authors":"Tim Stüdemann, Barbora Schwarzová, Till Schneidewind, Birgit Geertz, Constantin von Bibra, Marie Nehring, Judith Rössinger, J Simon Wiegert, Thomas Eschenhagen, Florian Weinberger","doi":"10.1016/j.stemcr.2024.06.012","DOIUrl":"10.1016/j.stemcr.2024.06.012","url":null,"abstract":"Transplantation of pluripotent stem cell-derived cardiomyocytes is a novel promising cell-based therapeutic approach for patients with heart failure. However, engraftment arrhythmias are a predictable life-threatening complication and represent a major hurdle for clinical translation. Thus, we wanted to experimentally study whether impulse generation by transplanted cardiomyocytes can propagate to the host myocardium and overdrive the recipient rhythm. We transplanted human induced pluripotent stem cell-derived cardiomyocytes expressing the optogenetic actuator Bidirectional Pair of Opsins for Light-induced Excitation and Silencing (BiPOLES) in a guinea pig injury model. Eight weeks after transplantation ex vivo, Langendorff perfusion was used to assess electrical coupling. Pulsed photostimulation was applied to specifically activate the engrafted cardiomyocytes. Photostimulation resulted in ectopic pacemaking that propagated to the host myocardium, caused non-sustained arrhythmia, and stimulated the recipient heart with higher pacing frequency (4/9 hearts). Our study demonstrates that transplanted cardiomyocytes can (1) electrically couple to the host myocardium and (2) stimulate the recipient heart. Thus, our results provide experimental evidence for an important aspect of engraftment-induced arrhythmia induction and thereby support the current hypothesis that cardiomyocyte automaticity can serve as a trigger for ventricular arrhythmias.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767473","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}

引用次数: 0

JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis. JAK/STAT 信号转导促进了溃疡性结肠炎独特细胞状态的出现。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-18 DOI: 10.1016/j.stemcr.2024.06.006

Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B Jensen

{"title":"JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis.","authors":"Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B Jensen","doi":"10.1016/j.stemcr.2024.06.006","DOIUrl":"10.1016/j.stemcr.2024.06.006","url":null,"abstract":"The intestinal epithelium ensures uptake of vital nutrients and acts as a barrier between luminal contents and the underlying immune system. In inflammatory bowel diseases, such as ulcerative colitis (UC), this barrier is compromised, and patients experience debilitating symptoms. Here, we perform single-cell RNA profiling of epithelial cells and outline patterns of cell fate decisions in healthy individuals and UC patients. We demonstrate that patterns of hierarchical behavior are altered in UC patients and identify unique cellular states associated with Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation in ulcerated and non-ulcerated areas of the colonic epithelium. These transcriptional changes could be recapitulated in human colonic organoids, wherein cytokine-mediated activation of JAK/STAT led to the emergence of cell populations with augmented regenerative properties. Altogether, our findings indicate that intricate relationships between epithelial and cytokine signaling regulate cell fate during epithelial tissue regeneration in humans and have important implications for the understanding of UC biology.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727879","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}

引用次数: 0