Stem Cell Reports最新文献

Methylome profiling of SetDB1-deficient ESCs reveals coordinated epigenetic cross-talk during pluripotency. setdb1缺陷ESCs的甲基组分析揭示了多能性过程中协调的表观遗传串扰。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103075

Nick G P Bovee, Ehsan Habibi, Zicong Liu, Stefan H A Hoogland, Siebren Frölich, Daniëlle Diepenbroek, Kim C M Bosman, Julia Arand, Irina A Maksakova, Anouk Klein Kranenbarg, Jörn Walter, Arie B Brinkman, Klaas W Mulder, Joop H Jansen, Michiel Vermeulen, Matthew Lorincz, Hendrik G Stunnenberg, Hendrik Marks

{"title":"Methylome profiling of SetDB1-deficient ESCs reveals coordinated epigenetic cross-talk during pluripotency.","authors":"Nick G P Bovee, Ehsan Habibi, Zicong Liu, Stefan H A Hoogland, Siebren Frölich, Daniëlle Diepenbroek, Kim C M Bosman, Julia Arand, Irina A Maksakova, Anouk Klein Kranenbarg, Jörn Walter, Arie B Brinkman, Klaas W Mulder, Joop H Jansen, Michiel Vermeulen, Matthew Lorincz, Hendrik G Stunnenberg, Hendrik Marks","doi":"10.1016/j.stemcr.2026.103075","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103075","url":null,"abstract":"SetDB1 is best known for catalyzing H3K9me3, but it also influences H3K27me3 deposition, CTCF-binding, and DNA methylation (DNAme). Given the interplay between DNAme and the other epigenetic features, we profiled DNAme following Setdb1 knockout (KO) in ground-state and serum-grown mouse embryonic stem cells (ESCs) to illuminate DNAme-dependent and -independent functions of SetDB1. Time-course whole-genome bisulfite sequencing of serum-grown ESCs shows that nearly half of SetDB1 binding sites are enriched with DNAme and H3K9me3, primarily at retrotransposons. Upon Setdb1 KO, both H3K9me3 and DNAme are reduced, with DNAme rapidly removed at many sites by TET enzymes. Some retrotransposons, primarily IAPs, are TET-resistant and lose DNAme slowly via passive dilution. Notably, SetDB1-mediated regulation of H3K27me3, CTCF-binding, and SMAD3 are uncoupled from the DNAme-H3K9me3 axis, and from each other. AlphaFold modeling and co-immunoprecipitation mass spectrometry suggest this uncoupling involves competitive binding to distinct SetDB1 protein domains, highlighting the complex coordination underlying SetDB1 functions.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103075"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From consent to participatory governance: The need for multi-stakeholder alignment in iPSC-based drug repurposing. 从同意到参与式治理：多方利益相关者在基于ipsc的药物再利用中保持一致的必要性。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103062

Esther A M Bührman, Alain Geille, Martina C Cornel, Wouter P C Boon, Vivi M Heine, Tessel Rigter

{"title":"From consent to participatory governance: The need for multi-stakeholder alignment in iPSC-based drug repurposing.","authors":"Esther A M Bührman, Alain Geille, Martina C Cornel, Wouter P C Boon, Vivi M Heine, Tessel Rigter","doi":"10.1016/j.stemcr.2026.103062","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103062","url":null,"abstract":"Induced pluripotent stem cells (iPSCs) are increasingly used as disease models to accelerate drug repurposing, especially for rare diseases. While ethical and regulatory issues in iPSC research have been widely discussed, little is known about how these challenges are addressed in practice. To provide insights into the current practice, challenges, and opportunities in the governance of research on iPSC-based drug repurposing for rare neurological disorders, semi-structured interviews were conducted with various experts from eight countries in the context of the SIMPATHIC project. The results indicate that this research context requires improved information provision for minors and individuals with cognitive impairment and more clarity regarding commercial use and reporting of findings. Uncertainty in governance procedures hinders collaboration, validation, and clinical translation in iPSC-based drug repurposing. Responsible (re)use of iPSCs requires dynamic, transparent, and participatory governance structures based on shared decision-making with all stakeholders involved.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103062"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Scalable generation of T lymphocytes from human pluripotent stem cells in suspended organoids. 人多能干细胞在悬浮类器官中可扩展生成T淋巴细胞。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103076

Qi Lei, Yudi Miao, Feng Zheng, Ruoqi Cheng, Yating Mo, Weifeng Lai, Zhengyang Zhou, Lejun Lv, Yuanyuan He, Huangfan Xie, Chenyi Dai, Yingfeng Zhang, Zixin Zhao, Mengxin Liu, Lemei Jia, Jun Xu, Cheng Li, Hongkui Deng, Chengyan Wang

{"title":"Scalable generation of T lymphocytes from human pluripotent stem cells in suspended organoids.","authors":"Qi Lei, Yudi Miao, Feng Zheng, Ruoqi Cheng, Yating Mo, Weifeng Lai, Zhengyang Zhou, Lejun Lv, Yuanyuan He, Huangfan Xie, Chenyi Dai, Yingfeng Zhang, Zixin Zhao, Mengxin Liu, Lemei Jia, Jun Xu, Cheng Li, Hongkui Deng, Chengyan Wang","doi":"10.1016/j.stemcr.2026.103076","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103076","url":null,"abstract":"Human pluripotent stem cells (hPSCs) are a promising cell source for producing T cells for regenerative medicine and immunotherapy. However, it is challenging to develop a scalable suspension culture system for generating functional T lymphocytes from hPSCs. Here, we developed a Matrigel-based artificial thymic organoid (Gel-ATO) system by encapsulating hPSC-derived induced hematopoietic progenitor cells (iHPCs) with MS5-hDLL4 stromal cells. The resulting Gel-ATOs produced functional iT cells capable of antigen-specific cytotoxicity in vitro and tumor suppression in vivo. Building on this system, we further established a rotating suspension culture to robustly generate iT lymphocytes with nearly 20-fold enhancement of iT cells production compared to stationary suspension culture. Importantly, these rotating suspension culture-derived iT cells were functional, exhibiting cytokine secretion, proliferation, and cytotoxicity. By addressing the dual requirements of scalability and function, our work paves the way for future clinical production of T cells for T cell-based cell therapy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103076"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revisiting patient protection in unproven cell and gene therapies under Japan's safety act. 根据日本安全法，重新审视未经证实的细胞和基因疗法对患者的保护。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103077

Kayo Takashima, Michael Morrison, Andrew J T George, Jusaku Minari

引用次数: 0

Insulin receptor substrate 2 regulates placental syncytiotrophoblast differentiation at the maternal-fetal interface. 胰岛素受体底物2在母胎界面调节胎盘合胞滋养细胞分化。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103061

Johanna Grinat, María Moya-Navamuel, Paula Blanco-Cueto, Claudia Alemán-Juanes, Nathaly Hernández-Díaz, Maravillas Mellado-López, Amparo Galán, Luke A Noon, Deborah J Burks, Katrien De Clercq, Jorge López-Tello, Vicente Pérez-García

{"title":"Insulin receptor substrate 2 regulates placental syncytiotrophoblast differentiation at the maternal-fetal interface.","authors":"Johanna Grinat, María Moya-Navamuel, Paula Blanco-Cueto, Claudia Alemán-Juanes, Nathaly Hernández-Díaz, Maravillas Mellado-López, Amparo Galán, Luke A Noon, Deborah J Burks, Katrien De Clercq, Jorge López-Tello, Vicente Pérez-García","doi":"10.1016/j.stemcr.2026.103061","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103061","url":null,"abstract":"The placental labyrinth is the primary site of maternal-fetal exchange, and its disruption contributes to placental insufficiency and fetal growth restriction (FGR). Here, we identify insulin receptor substrate 2 (IRS2) as a key regulator of mouse placental labyrinth development. Irs2 is expressed in the syncytiotrophoblast (SynT) layers of the labyrinth, where it integrates growth factor signaling during placental morphogenesis. Loss of IRS2 disrupts labyrinth organization, causing defective SynT-II differentiation, impaired trophoblast fusion, and reduced fetal vascularization. Using CRISPR-Cas9-engineered Irs2-/- trophoblast stem cells, we show that IRS2 deficiency impairs upregulation of the SynT-II regulators Pparγ and Gcm1, disrupting SynT-II differentiation and sinusoidal trophoblast giant cell specification. Mechanistically, IRS2 relays insulin-like growth factor (IGF) signals through phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways to coordinate trophoblast proliferation, differentiation, and vascular morphogenesis. Human trophoblast stem cell differentiation and organoid analyses reveal IRS2 enrichment in the human syncytiotrophoblast (STB), indicating conserved expression at the human maternal-fetal interface.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103061"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo. SIRT1在体外促进内皮活性和成骨，并在体内改善与年龄相关的骨骼再生缺陷。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-03 DOI: 10.1016/j.stemcr.2026.103063

Shibo Liu, Jingjing Shao, Qiheng Yang, Hanghang Liu, Yao Liu, Zizhuo Zheng, En Luo

{"title":"SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo.","authors":"Shibo Liu, Jingjing Shao, Qiheng Yang, Hanghang Liu, Yao Liu, Zizhuo Zheng, En Luo","doi":"10.1016/j.stemcr.2026.103063","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103063","url":null,"abstract":"Understanding age-driven bone weakening mechanisms is essential for developing precision therapeutic strategies. This study systematically investigated skeletal aging, focusing on the critical decline of SIRT1 and its impact on type H vessels and osteogenic cells. We found that SIRT1 markedly enhanced both endothelial tube formation and osteogenic differentiation in senescent bone marrow-derived mesenchymal stem cell (BMSC)/human umbilical vein endothelial cell (HUVEC) co-cultures. In vivo validation studies revealed that pharmacological activation of SIRT1 significantly improved bone regeneration in age-related osteoporotic defects in both femoral and mandibular sites. Mechanistically, β-catenin served as a downstream mediator of these effects in our experimental systems, with SIRT1 promoting β-catenin deacetylation and nuclear translocation to activate Wnt signaling. By demonstrating that SIRT1 enhances both endothelial and osteogenic functions in the aged bone microenvironment, this work provides a rationale for targeted bone rejuvenation strategies and mechanistically informed therapeutic innovation against geriatric osteoporosis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103063"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells. 骨髓激发的dll1提呈微粒增强小鼠造血干细胞和祖细胞的不对称分裂和维持。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-27 DOI: 10.1016/j.stemcr.2026.103059

Li Wenjing, Feng Yiting, Han Dongbo, Ao Yanxiao, Michael W Chen, Li Ning, Jin Yuhong, Liang Haiwei, Liu Wen, Zhu Xiaoyu, Du Yanan

{"title":"Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells.","authors":"Li Wenjing, Feng Yiting, Han Dongbo, Ao Yanxiao, Michael W Chen, Li Ning, Jin Yuhong, Liang Haiwei, Liu Wen, Zhu Xiaoyu, Du Yanan","doi":"10.1016/j.stemcr.2026.103059","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103059","url":null,"abstract":"Understanding the regulation of hematopoietic stem and progenitor cell (HSPC) fate and translating it into effective culture strategies remains a significant challenge. Asymmetric lysosomal inheritance during HSPC division has been shown to predict variations in daughter cell activity and fate, yet the underlying regulators remain unclear. Through cell-cell communication analysis of bone marrow single-cell sequencing data, we identified the Notch ligand Delta-like protein 1 (DLL1) as a potential regulator in HSPC asymmetric division (ACD). Interactions between DLL1-presenting microparticles (MP-Ds) and HSPCs were observed in addressable microwell arrays, simulating cellular responses to localized niche signals. Long-term single-cell tracking revealed that MP-D interactions polarized HSPC lysosomes toward the contact site, directing division orientation and consequent asymmetric lysosomal inheritance in paired daughter cells. Furthermore, this co-culture system enhanced long-term hematopoietic reconstitution capacity of HSPCs in serial transplantations. Our findings support an association between HSPC ACD and the presentation mode of DLL1 signals, which enhances the ex vivo maintenance of HSPCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103059"},"PeriodicalIF":5.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of effector CD4⁺ T cells from human iPSC. 从人iPSC中产生效应CD4+ T细胞。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-27 DOI: 10.1016/j.stemcr.2026.103058

Julian Amirault, Dar Heinze, Mengwei Yang, Charles M Kerr, Pushpinder S Bawa, Laura Polanco, Gabriel M Sgambettera, Feiya Wang, Anna C Belkina, Jennifer E Snyder-Cappione, Gustavo Mostoslavsky

{"title":"Generation of effector CD4+ T cells from human iPSC.","authors":"Julian Amirault, Dar Heinze, Mengwei Yang, Charles M Kerr, Pushpinder S Bawa, Laura Polanco, Gabriel M Sgambettera, Feiya Wang, Anna C Belkina, Jennifer E Snyder-Cappione, Gustavo Mostoslavsky","doi":"10.1016/j.stemcr.2026.103058","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103058","url":null,"abstract":"Off-the-shelf T cell therapies could be transformative in chimeric antigen receptor (CAR) therapies for cancers and treatment of chronic inflammatory diseases. However, challenges remain in generating CD4+ T cells from induced pluripotent stem cells (iPSCs). We describe a key role for the withdrawal of Notch ligand during T cell receptor stimulation of CD4/CD8 double-positive progenitors allowing access to the CD4+ lineage in iPSC T cells (iCD4+ T cells). Functional analyses of iCD4+ T cells by using a novel high-parameter cytometry by time-of-flight (CyTOF) intracellular cytokine panel revealed canonical Th1 cytokine signatures and cells producing varying combinations of other cytokines, including IL-4, IL-8, and IL-13. Single-cell RNA sequencing of iCD4+ T cells demonstrated a transcriptional signature similar to human peripheral CD4+ T cells. We believe this robust yet simple platform represents a key step toward off-the-shelf iCD4+ T cell therapies with utility for the treatment of a panoply of diseases including cancer and inflammatory autoimmune disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103058"},"PeriodicalIF":5.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage. CRISPR激活揭示SOX5/6/9是引导ipsc衍生细胞向脊索谱系发展的关键转录调控因子。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-27 DOI: 10.1016/j.stemcr.2026.103060

Xiaole Tong, Marieke Visscher, Frank M Riemers, Danielle Versluis, Niels Geijsen, Peng Shang, Marianna A Tryfonidou, Deepani W Poramba-Liyanage

{"title":"CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.","authors":"Xiaole Tong, Marieke Visscher, Frank M Riemers, Danielle Versluis, Niels Geijsen, Peng Shang, Marianna A Tryfonidou, Deepani W Poramba-Liyanage","doi":"10.1016/j.stemcr.2026.103060","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103060","url":null,"abstract":"Intervertebral disc (IVD) degeneration, a leading cause of chronic lower back pain, is associated with loss of vacuolated notochordal cells (NCs) and fibrotic remodeling of the nucleus pulposus. Emerging therapies increasingly focus on NCs, which are rare but therapeutically relevant cells for regenerating degenerated IVDs. In this study, we used CRISPR-based transactivation (CRISPRa) to direct the differentiation of human induced pluripotent stem cells (iPSCs) into the NC lineage. We tested CRISPRa-mediated activation of NOTO, TBXT, FOXA2, SOX5, SOX6, and SOX9, coupled with single-cell sequencing of Aggrecan-2A-mScarlet reporter iPSCs. This approach identified the SOX5/6/9 combination (SOX-trio) as critical for promoting NC lineage commitment. The SOX-trio yielded the largest cell population expressing a range of genes previously associated with NC identity, including SHH, FOXA1, FOXA2, FOXJ1, FN1, ALCAM, KRT8, and KRT18. Our study demonstrates the integration of CRISPRa with single-cell technologies as a powerful platform for investigating and enriching iPSC-derived NCs, supporting future regenerative strategies across various fields.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103060"},"PeriodicalIF":5.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Luck favors the prepared in hepatic conversion. 在肝脏转化中，幸运总是眷顾有准备的人。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-27 DOI: 10.1016/j.stemcr.2026.103057

Kate E Galloway

引用次数: 0