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Signaling reprogramming via Stat3 activation unravels high-fidelity human post-implantation embryo modeling 通过Stat3激活的信号重编程揭示了高保真的人类植入后胚胎建模
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-16 DOI: 10.1016/j.stem.2025.08.011
Chuanxin Chen, Jinyi Wu, Xinggu Wang, Litao Chang, Kexin Wang, Kaiyi Wu, Mingyue Guo, Huanhuan Li, Fei Sun, Xinxing Jiang, Yanlin Ma, Guangjin Pan, Zhenyu Xiao, José C.R. Silva
{"title":"Signaling reprogramming via Stat3 activation unravels high-fidelity human post-implantation embryo modeling","authors":"Chuanxin Chen, Jinyi Wu, Xinggu Wang, Litao Chang, Kexin Wang, Kaiyi Wu, Mingyue Guo, Huanhuan Li, Fei Sun, Xinxing Jiang, Yanlin Ma, Guangjin Pan, Zhenyu Xiao, José C.R. Silva","doi":"10.1016/j.stem.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.011","url":null,"abstract":"Human embryo models hold great promise for advancing medicine, but current systems lack efficiency and fidelity in replicating post-implantation stages. Here, we investigate whether STAT3 activation can reprogram pluripotent stem cells (PSCs) into early fates that self-organize into embryo models. Using a medium enhancing STAT3 activity (SAM), PSCs reprogram within 60 h into hypoblast, trophectoderm, naive epiblast, and extraembryonic mesoderm. Dissociating SAM-treated PSCs at 60–120 h, followed by 3D culture, results in dynamic development of post-implantation embryo-like structures with up to 52.41% ± 8.92% efficiency. Resulting day 6 examples resemble Carnegie stages 5 (CS5) to 7 (CS7) embryos, exhibiting bilaminar disc structure with epiblast and yolk sac, amniotic cavity, mesenchyme, chorionic cavity, and trophoblast. Notably, CS6/7-like examples exhibit gastrulation, including the formation and correct positioning of primitive streak, epithelial-to-mesenchymal transition, mesoderm, and definitive endoderm. The STAT3-mediated embryo model also closely aligns molecularly with CS6/7 embryo references and represents a state-of-the-art platform for advancing human embryogenesis research.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"28 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes 干性年龄相关性黄斑变性患者RPESC-RPE移植的安全性和耐受性：低剂量临床结果
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-16 DOI: 10.1016/j.stem.2025.08.012
Rajesh C. Rao, Brigitte L. Arduini, Susan Borden, Dhruv Sareen, Clive Svendsen, Paul Lee, Charles Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eric Oh, Shuna Park, Glenna Ford, Keith Dionne, Sally Temple, Jeffrey Stern
{"title":"Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes","authors":"Rajesh C. Rao, Brigitte L. Arduini, Susan Borden, Dhruv Sareen, Clive Svendsen, Paul Lee, Charles Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eric Oh, Shuna Park, Glenna Ford, Keith Dionne, Sally Temple, Jeffrey Stern","doi":"10.1016/j.stem.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.012","url":null,"abstract":"Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"67 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Human adult hippocampal neurogenesis is shaped by neuropsychiatric disorders, demographics, and lifestyle-related factors 成人海马神经发生受神经精神疾病、人口统计学和生活方式相关因素的影响
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-15 DOI: 10.1016/j.stem.2025.08.010
Berenice Márquez-Valadez, Marta Gallardo-Caballero, María Llorens-Martín
{"title":"Human adult hippocampal neurogenesis is shaped by neuropsychiatric disorders, demographics, and lifestyle-related factors","authors":"Berenice Márquez-Valadez, Marta Gallardo-Caballero, María Llorens-Martín","doi":"10.1016/j.stem.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.010","url":null,"abstract":"Adult hippocampal neurogenesis (AHN) regulates hippocampal-dependent functions and is targeted by physiological aging and neurodegenerative conditions. Patients with neuropsychiatric disorders show hippocampal abnormalities that might be related to changes in AHN. Here, we sought to determine whether major depression, schizophrenia, and bipolar disorder threaten the integrity of human AHN and the homeostasis of the dentate gyrus (DG) neurogenic niche—a specialized microenvironment in which new neurons grow. Our results show that the initial and intermediate stages of AHN, as well as distinct components of the niche, are selectively affected in these disorders. Demographics and various lifestyle-related factors (such as the consumption of alcohol and drugs of abuse) modulate both AHN and the cells that compose the niche, not only in patients with these disorders but also in neurologically healthy control individuals. These data might be relevant for the design of future strategies to treat and prevent mental health conditions.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"101 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Adopting novel alternative methods (NAMs) for biomedical research—What is the right approach? 采用新颖的替代方法（NAMs）进行生物医学研究-什么是正确的方法？
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-05 DOI: 10.1016/j.stem.2025.08.014
Clive N. Svendsen
{"title":"Adopting novel alternative methods (NAMs) for biomedical research—What is the right approach?","authors":"Clive N. Svendsen","doi":"10.1016/j.stem.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.014","url":null,"abstract":"<h2>Section snippets</h2><section><section></section></section><section><section><h2>Declaration of interests</h2>C.N.S. serves on the advisory board of <em>Cell Stem Cell</em>.</section></section>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"23 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Modeling the human maternal-fetal interface 人类母胎界面建模
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.08.004
Vladyslav Bondarenko, Margherita Yayoi Turco
{"title":"Modeling the human maternal-fetal interface","authors":"Vladyslav Bondarenko, Margherita Yayoi Turco","doi":"10.1016/j.stem.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.004","url":null,"abstract":"Stem cells and organoids enable the modeling of various aspects of human development <em>in vitro</em>, yet integrating them to study maternal-fetal interactions remains challenging. In this review, we explore the current <em>in vitro</em> models of the endometrium, placenta, and embryo and identify key challenges associated with their integration, including the establishment of morpho-functional complexity, spatiotemporal coordination, and appropriate <em>in vivo</em> benchmarking. We propose an interdisciplinary perspective that emphasizes a shift from “building blocks” to “building interactions.” Altogether, we provide a discussion on the challenges and prospects for advancing mechanistic understanding of intrauterine human development and the maternal-fetal interface.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"304 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Severing the scar supply line: CAR-T in chronic kidney disease 切断疤痕供给线：CAR-T治疗慢性肾脏疾病
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.08.002
Longwei Liu, Yingxiao Wang
{"title":"Severing the scar supply line: CAR-T in chronic kidney disease","authors":"Longwei Liu, Yingxiao Wang","doi":"10.1016/j.stem.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.002","url":null,"abstract":"CAR-T cell therapy is rapidly being extended to target various pathophysiological processes beyond cancer. In this issue of <em>Cell Stem Cell</em>, Zhao et al. engineered PDGFRβ-specific CAR-T cells <em>in vivo</em> to selectively target extracellular matrix-producing cells in kidney fibrosis,<span><span><sup>1</sup></span></span> opening new opportunities for treating fibrotic diseases with precision immunotherapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"29 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 β soloist to endocrine symphony: Subtype-complete islets conduct glucose harmony 从β独奏家到内分泌交响乐：亚型完全胰岛指挥葡萄糖和谐
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.08.001
Jia Zhao, Shenghui Liang, Timothy J. Kieffer
{"title":"From β soloist to endocrine symphony: Subtype-complete islets conduct glucose harmony","authors":"Jia Zhao, Shenghui Liang, Timothy J. Kieffer","doi":"10.1016/j.stem.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.001","url":null,"abstract":"While current stem cell differentiation protocols generate β cell-enriched islets that reverse hyperglycemia post-implantation, they can cause hypoglycemia. Meng et al.<span><span><sup>1</sup></span></span> reconstruct endocrine subtype-complete islets, which restore counterregulatory responses and protect against hypoglycemia in diabetic mice, highlighting the importance of endocrine diversity in designing physiologically regulated cell therapies for diabetes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"104 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging 纳米生物反应器检测空间相关造血干细胞和祖细胞衰老
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.07.013
Jessica Pham, Jane Isquith, Larisa Balaian, Shuvro P. Nandi, Claire Engstrom, Karla Mack, Inge van der Werf, Patrick Chang, Jana Stoudemire, Luisa Ladel, Emma Klacking, Antonio Ruiz, Daisy Chilin-Fuentes, Jenna Sneifer, David Mays, Paul Gamble, Shelby Giza, Jiya Janowitz, Trevor Nienaber, Tejaswini Mishra, Catriona H.M. Jamieson
{"title":"Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging","authors":"Jessica Pham, Jane Isquith, Larisa Balaian, Shuvro P. Nandi, Claire Engstrom, Karla Mack, Inge van der Werf, Patrick Chang, Jana Stoudemire, Luisa Ladel, Emma Klacking, Antonio Ruiz, Daisy Chilin-Fuentes, Jenna Sneifer, David Mays, Paul Gamble, Shelby Giza, Jiya Janowitz, Trevor Nienaber, Tejaswini Mishra, Catriona H.M. Jamieson","doi":"10.1016/j.stem.2025.07.013","DOIUrl":"https://doi.org/10.1016/j.stem.2025.07.013","url":null,"abstract":"Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team developed bone marrow niche nanobioreactors with lentiviral bicistronic fluorescent, ubiquitination-based cell-cycle indicator (FUCCI2BL) reporter for real-time HSPC tracking in artificial intelligence (AI)-driven CubeLabs. In month-long International Space Station (ISS) missions (SpX-24, SpX-25, SpX-26, and SpX-27) compared with ground controls, FUCCI2BL reporter, whole-genome and transcriptome sequencing, and cytokine arrays demonstrated cell-cycle, inflammatory cytokine, mitochondrial gene, human repetitive element, and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) deregulation together with clonal hematopoietic mutations. Furthermore, HSPC functionally organized multi-omics aging (HSPC-FOMA) analyses revealed reduced telomere maintenance, adenosine deaminase acting on RNA1 (ADAR1) p150 self-renewal gene expression, and replating capacity indicative of space-associated HSPC aging that may limit long-duration spaceflight.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"35 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Ready, set, but no go: Skin fat comes preloaded with waiting precursors 准备好了，准备好了，但还没有开始：皮肤脂肪预先装载了等待的前体
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.08.003
Jung-Won Shin, Maksim V. Plikus
{"title":"Ready, set, but no go: Skin fat comes preloaded with waiting precursors","authors":"Jung-Won Shin, Maksim V. Plikus","doi":"10.1016/j.stem.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.003","url":null,"abstract":"Fat depots across the body dynamically tune their sizes in response to nutrient demands and nonmetabolic cues. Writing in <em>Cell Stem Cell</em>, Rivera-Gonzalez et al.<span><span><sup>1</sup></span></span> report that skin fat, notable for its ability to rapidly expand, harbors molecularly distinct precursors, primed for proliferation and differentiation into mature adipocytes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Engineered VTA dopaminergic neurons offer a new path to treating depression 工程VTA多巴胺能神经元为治疗抑郁症提供了一条新的途径
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-09-04 DOI: 10.1016/j.stem.2025.08.007
Rossella Ventura
{"title":"Engineered VTA dopaminergic neurons offer a new path to treating depression","authors":"Rossella Ventura","doi":"10.1016/j.stem.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.007","url":null,"abstract":"Dysfunction of A10 midbrain dopaminergic (mDA) neurons is linked to psychiatric disorders, such as depression. In this issue, Yan et al.<span><span><sup>1</sup></span></span> present an efficient method for differentiating human pluripotent stem cells into A10-like mDA neurons. Activation of grafted A10-like neurons into the mouse mesolimbic circuit alleviates depression-like symptoms.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"33 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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