Stem Cell Reports最新文献_第2页

Post-transcriptional regulation maintains neurogenic potential of human neural progenitor cells. 转录后调控维持人类神经祖细胞的神经发生潜能。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-17 DOI: 10.1016/j.stemcr.2026.103082

Natasha M Méndez-Albelo, Yajie Zhang, Soraya O Sandoval, Yu Guo, Yu Gao, Lily A Peters, Carissa L Sirois, Anna B Widicus, Paofue Yang, Drew N Trygstad, Magnus T Eckholm, Zhiyan Xu, Riley V Smith, Rachel M Disher, Christian J Johnston, Xinyu Zhao

{"title":"Post-transcriptional regulation maintains neurogenic potential of human neural progenitor cells.","authors":"Natasha M Méndez-Albelo, Yajie Zhang, Soraya O Sandoval, Yu Guo, Yu Gao, Lily A Peters, Carissa L Sirois, Anna B Widicus, Paofue Yang, Drew N Trygstad, Magnus T Eckholm, Zhiyan Xu, Riley V Smith, Rachel M Disher, Christian J Johnston, Xinyu Zhao","doi":"10.1016/j.stemcr.2026.103082","DOIUrl":"10.1016/j.stemcr.2026.103082","url":null,"abstract":"Increasing evidence supports important roles of post-transcriptional regulation in brain development; however, the precise mechanism remains unclear. Here, we show that Fragile X autosomal homolog 1 (FXR1), a brain-enriched RNA-binding protein (RBP), is essential for human neurogenesis. FXR1-deficient human cortical neural progenitor cells (NPCs) have reduced proliferation and impaired cell cycle exit during differentiation, leading to impaired neuronal differentiation. Transcriptomic and co-expression network analyses revealed FXR1 as an orchestrator of stage-specific gene programs driving neural differentiation. High-mobility group protein B2 (HMGB2), a master transcriptional regulator in stem cells, is a direct target of FXR1. FXR1 and HuR co-regulate HMGB2 mRNA, and their opposing actions on mRNA stability maintain the levels of HMGB2 in human NPCs. Reducing HMGB2 levels in FXR1-deficient NPCs rescues NPC proliferation and neuronal differentiation. Together, these findings establish post-transcriptional regulation as a key mechanism that maintains neurogenic potency of human NPCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103082"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991513","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

Quality control and non-clinical testing of iPSC- and ESC-derived medicinal products: A systematic review. iPSC和esc衍生药品的质量控制和非临床检测：系统综述。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-24 DOI: 10.1016/j.stemcr.2026.103084

Akvilė Gasiūnaitė, Mara Tihaya, Inge van Amerongen-Westra, Fong Lin, Pema Gurung, Bahareh Rajaei, Eelco de Koning, Françoise Carlotti, Pauline Meij

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 : 2026-10-13 Epub 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":"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":"2026-10-13","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

The crosstalk between alternative splicing and histone ubiquitination modulates fast chemical reprogramming to pluripotency. 选择性剪接和组蛋白泛素化之间的串扰调节了快速化学重编程到多能性。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-24 DOI: 10.1016/j.stemcr.2026.103089

Qian Deng, Xi Chen, Yuhan Li, Yixin Wang, Yueqing He, Dylan Zhu, Guo Chen, Saiyong Zhu

{"title":"The crosstalk between alternative splicing and histone ubiquitination modulates fast chemical reprogramming to pluripotency.","authors":"Qian Deng, Xi Chen, Yuhan Li, Yixin Wang, Yueqing He, Dylan Zhu, Guo Chen, Saiyong Zhu","doi":"10.1016/j.stemcr.2026.103089","DOIUrl":"10.1016/j.stemcr.2026.103089","url":null,"abstract":"Cellular reprogramming has revolutionized regenerative medicine. Recently, we develop a fast chemical reprogramming (FCR) system; however, the underlying molecular mechanisms remain largely unknown. Here, we investigated the dynamics of RNA-binding protein (RBP) expression and alternative splicing (AS) events in the FCR system. We found that knockdown of AS regulator PTBP3 significantly enhanced FCR efficiency. Mechanistically, we identified that the PTBP3-SCMH1 axis regulated multiple downstream pathways, including inflammatory pathway. Pharmacological inhibition of inflammatory pathway using Amlexanox and BMS-345541 could further improve FCR efficiency. Collectively, our results highlight the essential role of AS in FCR and suggest that the crosstalk between AS and histone ubiquitination mediated by PTBP3-SCMH1 axis can be harnessed for modulating cell fates. These studies will help to better understand the fascinating question of how small molecules alone can rapidly induce pluripotency and provide new approaches for regeneration and rejuvenation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103089"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040626","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

Voices: What impact has iPSC technology had on your research and/or field? 声音：iPSC技术对你的研究和/或领域有什么影响？

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-10-01 DOI: 10.1016/j.stemcr.2026.103110

引用次数: 0

Photoreceptor replacement therapy using a tissue scaffold shows evidence of donor-host integration in non-human primate retina. 使用组织支架的光感受器替代疗法显示了非人类灵长类动物视网膜供体-宿主整合的证据。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 DOI: 10.1016/j.stemcr.2026.103079

Laura Patak, Soumaya Belhadj, Agustin Luz-Madrigal, Praveen Joseph Susaimanickam, Jennifer M LaPorta, Tsung-Han Tsai, Ruosen Xie, Jacqueline Gayet, Hector C Baez, William S Fischer, Rachel Hollar, Nathaniel Foley, Andrea L Campbell, Shaoqin Gong, Zhenqiang Ma, Arvydas Maminishkis, Kapil Bharti, Juan Amaral, Vamsi K Gullapalli, David A DiLoreto, David M Gamm, Teresa Puthussery, Juliette E McGregor

{"title":"Photoreceptor replacement therapy using a tissue scaffold shows evidence of donor-host integration in non-human primate retina.","authors":"Laura Patak, Soumaya Belhadj, Agustin Luz-Madrigal, Praveen Joseph Susaimanickam, Jennifer M LaPorta, Tsung-Han Tsai, Ruosen Xie, Jacqueline Gayet, Hector C Baez, William S Fischer, Rachel Hollar, Nathaniel Foley, Andrea L Campbell, Shaoqin Gong, Zhenqiang Ma, Arvydas Maminishkis, Kapil Bharti, Juan Amaral, Vamsi K Gullapalli, David A DiLoreto, David M Gamm, Teresa Puthussery, Juliette E McGregor","doi":"10.1016/j.stemcr.2026.103079","DOIUrl":"10.1016/j.stemcr.2026.103079","url":null,"abstract":"Retinal degeneration is characterized by progressive photoreceptor (PR) loss, leading to visual impairment and ultimately blindness. PR replacement is a promising therapeutic strategy, but surgical delivery remains challenging, and efficacy in primates remains unknown. Tissue scaffolds hold potential for better control over cell delivery and distribution. Here, we delivered a scaffold, loaded with human embryonic stem-cell-derived PR precursors (PRPs), to the subretinal space of a non-human primate (NHP) and monitored donor PR survival and morphology in vivo. A substantial fraction of donor PRs survived for 20-weeks, with neurite extension by week 7 and some morphological elongation by week 17. Immunolabeling confirmed donor PR survival at 20 weeks with expression of key phototransduction and ribbon proteins, and some donor PRs forming putative synapses with host bipolar cells (BCs), including midget BCs. These findings suggest that scaffold-mediated PR replacement holds promise for restoring high acuity foveal vision.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"21 10","pages":"103079"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184282","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

Chemical induction and reversal of photoreceptor dystrophy in retinal organoids. 视网膜类器官光感受器营养不良的化学诱导和逆转。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-10 DOI: 10.1016/j.stemcr.2026.103078

Allyssa Bradley, Hyejung Min, Soyoung Park, William Temme, Soyeon Park, Ahmad Al-Moujahed, Eun-Jin Lee, Jonathan H Lin

{"title":"Chemical induction and reversal of photoreceptor dystrophy in retinal organoids.","authors":"Allyssa Bradley, Hyejung Min, Soyoung Park, William Temme, Soyeon Park, Ahmad Al-Moujahed, Eun-Jin Lee, Jonathan H Lin","doi":"10.1016/j.stemcr.2026.103078","DOIUrl":"10.1016/j.stemcr.2026.103078","url":null,"abstract":"Activating transcription factor 6 (ATF6) controls a signal transduction pathway of the unfolded protein response (UPR). Loss-of-function ATF6 mutations cause inherited photoreceptor diseases. Ceapin-A7 is a non-toxic, cell-permeable small molecule that selectively inhibits ATF6. We investigated how ATF6 inhibition impacts photoreceptors by treating wild-type human retinal organoids with Ceapin-A7 and evaluating the effects via single-nucleus RNA sequencing (snRNA-seq) and microscopy after 2 months. Ceapin-A7 administration effectively suppressed ATF6-dependent and UPR-related gene expression and led to fewer rod and cone inner/outer segments, malformed/stunted cone segments, and Müller gliosis, while no photoreceptor cell death was observed. When Ceapin-A7 was removed from retinal organoid media after extended exposure, photoreceptor segment quantity increased, indicating that photoreceptors were able to restore segments. These findings demonstrate that ATF6 is selectively required for photoreceptor inner/outer segment integrity. Furthermore, chemically restoring ATF6 activity promotes photoreceptor segment growth, identifying ATF6/UPR signaling as an attractive pathway to treat photoreceptor diseases.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103078"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930903","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 : 2026-10-13 Epub 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":"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":"2026-10-13","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

PEX11β controls early neural progenitor fate through regulation of peroxisomal fission and lipid metabolism. PEX11β通过调节过氧化物酶体裂变和脂质代谢来控制早期神经祖细胞的命运。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-17 DOI: 10.1016/j.stemcr.2026.103080

C Bodnya, R P Theart, M E Colley, J M Spraggins, V Gama

{"title":"PEX11β controls early neural progenitor fate through regulation of peroxisomal fission and lipid metabolism.","authors":"C Bodnya, R P Theart, M E Colley, J M Spraggins, V Gama","doi":"10.1016/j.stemcr.2026.103080","DOIUrl":"10.1016/j.stemcr.2026.103080","url":null,"abstract":"Peroxisomes are metabolic organelles that undergo fission to maintain peroxisome number for lipid homeostasis and cellular function. The peroxisomal fission machinery is shared with mitochondria, and although mitochondrial fission regulates neural cell fate decisions during human neurogenesis, it remains unclear whether peroxisomal fission independently influences human neural development. PEX11β selectively regulates peroxisomal fission by promoting membrane deformation, elongation, and downstream fission factor recruitment. To uncouple mitochondrial and peroxisomal fission in early human neurogenesis, we generated PEX11β knockout iPSCs and tracked differentiation into neural progenitors and neural rosettes. At the cellular level, perturbing PEX11β selectively impaired peroxisomal lipid metabolism, characterized by reduced ether-linked phospholipids. At the tissue level, PEX11β deficiency altered neural rosette architecture, resulting in enlarged central lumens and expanded neural progenitor populations. This human neural model uncouples mitochondrial and peroxisomal fission and positions PEX11β as a distinct regulator of lipid metabolism and neural progenitor fate during human neurogenesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103080"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991455","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

Atypical cell cycle regulation over neural stem cell expansion. 非典型细胞周期对神经干细胞扩增的调控。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-19 DOI: 10.1016/j.stemcr.2026.103113

Dorota Lubanska, Ingrid Qemo, Keith Franklin Stringer, Hema Priya Mahendran, Bre-Anne Fifield, Alan Cieslukowski, Sami Alrashed, Youshaa El-Abed, Emmanuel Boujeke, Alexander Rodzinka, Elizabeth Fidalgo da Silva, Stephanie Dinescu, Alexandra Sorge, Srinath Kandalam, Dalton Liwanpo, Jillian Brown, Hasan Ghafoor, Maheen Arshad, Lisa A Porter

引用次数: 0