Stem Cell Reports最新文献_第9页

Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells. 利用干细胞衍生的α细胞模拟糖尿病α细胞功能障碍。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-08 DOI: 10.1016/j.stemcr.2025.102504

Swikriti Shrestha, Lauren T Jennings, Kyle Knofczynski, Sharath B Shivakumar, Quinn P Peterson

{"title":"Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells.","authors":"Swikriti Shrestha, Lauren T Jennings, Kyle Knofczynski, Sharath B Shivakumar, Quinn P Peterson","doi":"10.1016/j.stemcr.2025.102504","DOIUrl":"10.1016/j.stemcr.2025.102504","url":null,"abstract":"Dysfunction of pancreatic alpha cells contributes to the pathophysiology of diabetes. Features of diabetic alpha cell dysfunction include glucagon hypersecretion, defects in proglucagon processing, and altered transcriptomic profile. The lack of an in vitro human alpha cell model has prevented the investigation, and potential correction, of these dysfunctional phenotypes. Here, we show that induction of endoplasmic reticulum (ER) stress in stem cell-derived alpha (SC-α) cells induces hypersecretion of glucagon. ER stress also increases the secretion of glicentin and the expression of glucagon-like peptide-1 (GLP-1), peptides produced by alternate cleavage of proglucagon by the prohormone convertase 1 (PC1/3) enzyme. Additionally, ER stress establishes a diabetic transcriptional state in SC-α cells characterized by downregulation of MAFB, as well as glycolysis and oxidative phosphorylation pathways. We show that sunitinib, a tyrosine kinase inhibitor, protects SC-α cells against the ER stress-induced glucagon hypersecretion phenotype. Thus, SC-α cell model can advance our knowledge of islets in health and diabetes.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102504"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017629","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

Engineered proxies and the illusion of de-extinction. 精心设计的代理和消除灭绝的幻觉。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-15 DOI: 10.1016/j.stemcr.2025.102505

Dusko Ilic

引用次数: 0

How neural stem cell therapy promotes brain repair after stroke. 神经干细胞治疗如何促进脑卒中后的修复。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-22 DOI: 10.1016/j.stemcr.2025.102507

Rebecca Z Weber, Ruslan Rust, Christian Tackenberg

引用次数: 0

Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells. NANOG增强子的发现及其在人胚胎干细胞自我更新和分化中的重要作用。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-29 DOI: 10.1016/j.stemcr.2025.102511

Jielin Yan, Renhe Luo, Bess P Rosen, Dingyu Liu, Wilfred Wong, Christina S Leslie, Danwei Huangfu

{"title":"Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells.","authors":"Jielin Yan, Renhe Luo, Bess P Rosen, Dingyu Liu, Wilfred Wong, Christina S Leslie, Danwei Huangfu","doi":"10.1016/j.stemcr.2025.102511","DOIUrl":"10.1016/j.stemcr.2025.102511","url":null,"abstract":"Human embryonic stem cells (hESCs) are notable for their ability to self-renew and to differentiate into all tissue types in the body. NANOG is a core regulator of hESC identity, and dynamic control of its expression is crucial to maintain the balance between self-renewal and differentiation. Transcriptional regulation depends on enhancers, but NANOG enhancers in hESCs are not well characterized. Here, we report two NANOG enhancers discovered from a CRISPR interference screen in hESCs. Deletion of a single copy of either enhancer significantly reduced NANOG expression, compromising self-renewal and increasing differentiation propensity. Interestingly, these two NANOG enhancers are involved in a tandem duplication event found in certain primates including humans but not in mice. However, the duplicated counterparts do not regulate NANOG expression. This work expands our knowledge of functional enhancers in hESCs and highlights the sensitivity of the hESC state to the dosage of core regulators and their enhancers.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102511"},"PeriodicalIF":5.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188047","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

Stem cell fate decisions: Substates and attractors. 干细胞命运的决定：亚态和吸引子。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 DOI: 10.1016/j.stemcr.2025.102532

James E Mason, Xiaokai Nie, Daniel Coca, Peter W Andrews

引用次数: 0

Leveraging CRISPR activation for rapid assessment of gene editing products in human pluripotent stem cells. 利用CRISPR激活快速评估人类多能干细胞中的基因编辑产物。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-08 DOI: 10.1016/j.stemcr.2025.102499

Youjun Wu, Aaron Zhong, Alessandro Evangelisti, Mega Sidharta, Huangfu Danwei, Lorenz Studer, Ting Zhou

{"title":"Leveraging CRISPR activation for rapid assessment of gene editing products in human pluripotent stem cells.","authors":"Youjun Wu, Aaron Zhong, Alessandro Evangelisti, Mega Sidharta, Huangfu Danwei, Lorenz Studer, Ting Zhou","doi":"10.1016/j.stemcr.2025.102499","DOIUrl":"10.1016/j.stemcr.2025.102499","url":null,"abstract":"Verification of genome editing in human pluripotent stem cells (hPSCs), particularly at silent loci, is desirable but challenging, as it often requires complex and time-intensive differentiation to induce their expression. Here, we establish a rapid and effective workflow for verifying genome-edited hPSC lines targeting unexpressed genes using CRISPR-mediated transcriptional activation (CRISPRa). We systematically compared the efficiency of various CRISPRa systems and identified the synergistic activation mediator (SAM) system as the most potent for activating silent genes in hPSCs. Furthermore, combining SAM with TET1, a demethylation module, enhanced the activation of methylated genes. By inducing targeted gene activation in undifferentiated hPSCs using CRISPRa, we successfully verified single- and dual-reporter lines, functionally tested degradation tag (dTAG) knockins, and validated silent gene knockouts within 48 h. This approach bypasses the need to induce target gene expression through differentiation, providing a rapid and effective assay for verifying silent gene editing at the hPSC stage.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102499"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038265","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 competition eliminates aneuploid human pluripotent stem cells. 细胞竞争消除了非整倍体人类多能干细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-22 DOI: 10.1016/j.stemcr.2025.102506

Amanda Ya, Chenhui Deng, Kristina M Godek

{"title":"Cell competition eliminates aneuploid human pluripotent stem cells.","authors":"Amanda Ya, Chenhui Deng, Kristina M Godek","doi":"10.1016/j.stemcr.2025.102506","DOIUrl":"10.1016/j.stemcr.2025.102506","url":null,"abstract":"Human pluripotent stem cells (hPSCs) maintain diploid populations for generations despite frequent mitotic errors that cause aneuploidy or chromosome imbalances. Consequently, aneuploid hPSC propagation must be prevented to sustain genome stability, but how this is achieved is unknown. Surprisingly, we find that, unlike somatic cells, uniformly aneuploid hPSC populations with heterogeneous abnormal karyotypes proliferate. Instead, in mosaic populations, cell-non-autonomous competition between neighboring diploid and aneuploid hPSCs eliminates less fit aneuploid cells, regardless of specific chromosome imbalances. Aneuploid hPSCs with lower MYC or higher p53 levels relative to diploid neighbors are outcompeted but conversely gain an advantage when MYC and p53 relative abundance switches. Thus, MYC- and p53-driven cell competition preserves hPSC genome integrity despite their low mitotic fidelity and intrinsic capacity to proliferate with an aneuploid genome. These findings have important implications for using hPSCs in regenerative medicine and for how diploid human embryos form during development despite the prevalence of aneuploidy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102506"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133292","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

An analysis of stem cell training programs for physicians in the US-A mirage of credibility. 对美国医生干细胞培训项目的分析——可信度的海市蜃楼。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-29 DOI: 10.1016/j.stemcr.2025.102510

Luqman Ellythy, Mohamed Addani, Zubin Master

引用次数: 0

A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling. 锌指依赖、prdm13驱动的机制通过WNT信号调节小鼠胚胎干细胞的视网膜祖细胞命运。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-22 DOI: 10.1016/j.stemcr.2025.102508

Brian W Basinski, Yuanhao Huang, Qiang Li, Charukesi D Sivakumar, Tyler J Carman, Hana M Pan, Jing Xu, D Ford Hannum, Jie Liu, Rajesh C Rao

{"title":"A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling.","authors":"Brian W Basinski, Yuanhao Huang, Qiang Li, Charukesi D Sivakumar, Tyler J Carman, Hana M Pan, Jing Xu, D Ford Hannum, Jie Liu, Rajesh C Rao","doi":"10.1016/j.stemcr.2025.102508","DOIUrl":"10.1016/j.stemcr.2025.102508","url":null,"abstract":"The transcriptional regulation underlying eye field (retinal primordium) development requires precise control, yet the mechanisms guiding lineage-specific differentiation within the central nervous system (CNS) remain incompletely understood. Using neuroectoderm (NE) organoids derived from mouse embryonic stem cells, we investigate the role of PRDM13 in eye field specification. We demonstrate that Prdm13 expression inhibits RX+ eye field fate but permits non-eye field NE differentiation, an effect that depends on its first and second zinc-finger domains. Prdm13 activates the WNT/β-catenin signaling pathway during differentiation, leading to downregulation of key transcription factors crucial for establishing the eye field. Pharmacological inhibition of WNT signaling abolishes PRDM13-mediated suppression, restoring RX+ eye field differentiation. Our work reveals a previously undescribed PRDM13-WNT signaling axis that regulates lineage-specific neural differentiation of embryonic stem cells.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102508"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133290","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

Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells. 缺氧和GCM1表达缺失阻碍了人滋养细胞干细胞的分化和接触抑制。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-24 DOI: 10.1016/j.stemcr.2025.102481

Jessica K Cinkornpumin, Sin Young Kwon, Anna-Maria Prandstetter, Theresa Maxian, Jacinthe Sirois, James Goldberg, Joy Zhang, Deepak Saini, Purbasa Dasgupta, Mariyan J Jeyarajah, Stephen J Renaud, Soumen Paul, Sandra Haider, William A Pastor

{"title":"Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells.","authors":"Jessica K Cinkornpumin, Sin Young Kwon, Anna-Maria Prandstetter, Theresa Maxian, Jacinthe Sirois, James Goldberg, Joy Zhang, Deepak Saini, Purbasa Dasgupta, Mariyan J Jeyarajah, Stephen J Renaud, Soumen Paul, Sandra Haider, William A Pastor","doi":"10.1016/j.stemcr.2025.102481","DOIUrl":"10.1016/j.stemcr.2025.102481","url":null,"abstract":"During the first stages of embryonic development, the placenta develops under very low oxygen tension (∼1%-2% O2), so we sought to determine the regulatory role of oxygen in human trophoblast stem cells (hTSCs). We find that low oxygen promotes hTSC self-renewal but inhibits differentiation to syncytiotrophoblast (STB) and extravillous trophoblast (EVT). The transcription factor GCM1 (glial cell missing transcription factor 1) is downregulated in low oxygen, and concordantly, there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC likewise impaired EVT and STB formation. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed binding near key genes upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102481"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044611","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