Cell stem cell最新文献

TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency. TCA循环重新布线支持组蛋白乙酰化来源和细胞命运转变在幼稚多能性退出。

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-24 DOI: 10.1016/j.stem.2026.04.004

Eleni Kafkia,David Pladevall-Morera,Lidia Argemi-Muntadas,Gangqi Wang,Roberta Noberini,Arnau Casòliba-Melich,Sandra Bagés-Arnal,Matthias Anagho-Mattanovich,Rita Silvério-Alves,Johanna Gassler,Tiziana Bonaldi,Ton J Rabelink,Thomas Moritz,Jan Jakub Żylicz

{"title":"TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency.","authors":"Eleni Kafkia,David Pladevall-Morera,Lidia Argemi-Muntadas,Gangqi Wang,Roberta Noberini,Arnau Casòliba-Melich,Sandra Bagés-Arnal,Matthias Anagho-Mattanovich,Rita Silvério-Alves,Johanna Gassler,Tiziana Bonaldi,Ton J Rabelink,Thomas Moritz,Jan Jakub Żylicz","doi":"10.1016/j.stem.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.004","url":null,"abstract":"Metabolism shapes stem cell differentiation and epigenome regulation, especially during the exit from naive pluripotency in vitro. Yet how metabolic networks reorganize at implantation remains unclear. Here, we map metabolite routing in pre- and post-implantation mouse embryos and across dynamic pluripotency transitions in stem cells, revealing that the tricarboxylic acid (TCA) cycle undergoes spatio-temporal rewiring rather than a simple shutdown. Pyruvate emerges as a central metabolic nexus, where pyruvate carboxylase and malic enzyme activities create a cyclical carbon flow essential for balanced metabolic and transcriptional states, timely exit from naive pluripotency, and differentiation. As cells leave naive pluripotency, glutamine increasingly fuels the TCA cycle; unexpectedly, it is also the dominant carbon source for histone acetylation. The necessary acetyl-CoA is generated via IDH1-mediated reductive glutamine carboxylation and is coupled to pyruvate cycling, sustaining histone acetylation. These findings uncover a metabolically rewired, route-specific nutrient utilization program that links metabolism to epigenomic regulation and pluripotency transitions at implantation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"30 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147743739","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 CAR-monocytes coordinate fibrosis clearance and cardiac regeneration following myocardial infarction. 工程化car -单核细胞协调心肌梗死后的纤维化清除和心脏再生。

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-24 DOI: 10.1016/j.stem.2026.04.003

Zhenguo Wu,Xiaohan Zou,Chen Chen,Mengge Zhou,Xiao Yue,Dachuan Guo,Yunqian Gao,Chang Ma,Qingmei Han,Danning Yang,Dejin Zang,Ruicheng Song,Yifei Li,Shujie Pang,Haoran Ren,Wencheng Zhang,Meng Zhang,Yun Zhang,Jianmin Yang,Xinyi Jiang,Cheng Zhang

{"title":"Engineered CAR-monocytes coordinate fibrosis clearance and cardiac regeneration following myocardial infarction.","authors":"Zhenguo Wu,Xiaohan Zou,Chen Chen,Mengge Zhou,Xiao Yue,Dachuan Guo,Yunqian Gao,Chang Ma,Qingmei Han,Danning Yang,Dejin Zang,Ruicheng Song,Yifei Li,Shujie Pang,Haoran Ren,Wencheng Zhang,Meng Zhang,Yun Zhang,Jianmin Yang,Xinyi Jiang,Cheng Zhang","doi":"10.1016/j.stem.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.003","url":null,"abstract":"Overwhelming cardiomyocyte death and excessive cardiac fibrosis post myocardial infarction (MI) collectively lead to heart failure and mortality. For treating this devastating disease, it is essential to eliminate fibrosis and reconstitute the damaged myocardium, yet effective strategies remain elusive. Here, we created pleiotropic chimeric antigen receptor-monocytes (pCAR-Mos), revitalizing the injured heart via synergistic fibrosis clearance and myocardial reconstitution. Specifically, we engineered monocytes to express fibroblast activation protein (FAP)-chimeric antigen receptor (CAR) and secrete the cardioregenerative protein Agrin. CAR-mediated phagocytosis of myofibroblasts, which was further enhanced by Agrin, significantly attenuated fibrotic scar formation. Moreover, Agrin secretion promoted cardiomyocyte regeneration, thereby facilitating replenishment of functional myocardium. Treatment with pCAR-Mos remodeled the cardiac fibrotic microenvironment and substantially restored cardiac function in MI mice. In sum, our findings confirmed that pCAR-Mos exerted potent phagocytic activity against profibrotic myofibroblasts while simultaneously enabling myocardial reconstitution, thereby providing a reversible treatment strategy for MI with broad application in other fibrotic diseases.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"259 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147743742","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

Transcriptional profiles of immature neurons in aged human hippocampus track Alzheimer's pathology and cognitive resilience. 老年人类海马体中未成熟神经元的转录谱追踪阿尔茨海默病的病理和认知恢复能力。

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-24 DOI: 10.1016/j.stem.2026.04.002

Giorgia Tosoni,Dilara Ayyildiz,Sarah Snoeck,Elena P Moreno-Jiménez,Amber Penning,Estibaliz Santiago-Mujika,Olmo Ruiz Ormaechea,Hyunah Lee,Suresh Poovathingal,Kristofer Davie,Julien Bryois,Will Macnair,Jasper Anink,Luuk E De Vries,Sahand Farmand,Erik Nutma,Dick F Swaab,Eleonora Aronica,Jinte Middeldorp,Sandrine Thuret,Laurent Roybon,Onur Basak,Carlos P Fitzsimons,Paul J Lucassen,Evgenia Salta

{"title":"Transcriptional profiles of immature neurons in aged human hippocampus track Alzheimer's pathology and cognitive resilience.","authors":"Giorgia Tosoni,Dilara Ayyildiz,Sarah Snoeck,Elena P Moreno-Jiménez,Amber Penning,Estibaliz Santiago-Mujika,Olmo Ruiz Ormaechea,Hyunah Lee,Suresh Poovathingal,Kristofer Davie,Julien Bryois,Will Macnair,Jasper Anink,Luuk E De Vries,Sahand Farmand,Erik Nutma,Dick F Swaab,Eleonora Aronica,Jinte Middeldorp,Sandrine Thuret,Laurent Roybon,Onur Basak,Carlos P Fitzsimons,Paul J Lucassen,Evgenia Salta","doi":"10.1016/j.stem.2026.04.002","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.002","url":null,"abstract":"The existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain an open question. Although rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus both under healthy conditions and in Alzheimer's disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged healthy, AD, and dementia-resilient human hippocampus samples to probe immature neuronal signatures and gene expression alterations associated with AD pathology and resilience. By applying an integrated experimental and computational pipeline, we identified persistent populations of immature neurons across all donor groups, with transcriptional profiles reflecting \"juvenile\" cellular functions, which are compromised in AD. Our findings suggest that the presence of these immature neuronal populations per se may actively contribute to maintaining homeostasis within the aged human hippocampus and to cognitive resilience in AD.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"54 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147743741","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

MMRN1-EGFR drives sialylglycan-Siglec immune evasion in AML leukemia stem cells. MMRN1-EGFR驱动AML白血病干细胞的唾液聚糖- siglec免疫逃避。

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-23 DOI: 10.1016/j.stem.2026.03.012

Meixi Peng,Yongxiu Huang,Mengyun Zhang,Qinrong Yan,Lulu Li,Yaoqi Gui,Jingsong Cheng,Yanni Sun,Yi Mo,Wenqiong Xiang,Yongjie Zhang,Li Wang,Qin Wen,Xi Zhang,Yu Hou

{"title":"MMRN1-EGFR drives sialylglycan-Siglec immune evasion in AML leukemia stem cells.","authors":"Meixi Peng,Yongxiu Huang,Mengyun Zhang,Qinrong Yan,Lulu Li,Yaoqi Gui,Jingsong Cheng,Yanni Sun,Yi Mo,Wenqiong Xiang,Yongjie Zhang,Li Wang,Qin Wen,Xi Zhang,Yu Hou","doi":"10.1016/j.stem.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.stem.2026.03.012","url":null,"abstract":"Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) relapse and therapy resistance, predominantly through immune evasion. Here, we identify multimerin 1 (MMRN1) as being highly and specifically expressed in LSCs. Mechanistically, MMRN1 activates the epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 1 (STAT1) pathway via its epidermal growth factor (EGF)-like domain, suppressing Neu5Ac degradation to drive sialylglycan accumulation, which forms glycoimmune checkpoints functionally akin to programmed death 1 (PD-1)/the cytotoxic T-lymphocyte antigen-4 (CTLA-4). These sialylglycans activate the sialylglycan-Siglec immune checkpoint axis, impairing T/natural killer (NK) cell activity and enabling LSC immune evasion. Additionally, MMRN1 sustains LSC self-renewal via the EGFR/STAT5/CD9 pathway. Genetic ablation of MMRN1 markedly suppresses AML progression and synergizes with anti-PD-L1/CTLA-4 therapy. In a clinical trial (ChiCTR2500097714), erlotinib (an EGFR inhibitor) combined with azacitidine plus the HAG regimen, which consists of homoharringtonine, a low dose of cytarabine, and granulocyte colony-stimulating factor priming, achieves a remission rate of 75% in relapsed/refractory AML, likely via MMRN1/EGFR axis blockade. Our findings establish MMRN1 as a dual-functional target for LSC maintenance and immune evasion and propose that disrupting MMRN1 or EGFR remodels the immunosuppressive tumor microenvironment, offering a promising strategy for AML immunotherapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"67 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738947","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

Turning drivers into regulators: In vivo CAR reprogramming of Tfh cells 将驱动因子转化为调节因子：Tfh细胞的体内CAR重编程

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-02 DOI: 10.1016/j.stem.2026.03.011

Urmi Hofland, Maria Montes De Oca Arena, Laurence Morel

引用次数: 0

Reconstructing tumor tissues in 3D: From organoids to bioengineered niches 三维重建肿瘤组织：从类器官到生物工程生态位

IF 23.9 1区医学

Cell stem cell Pub Date : 2026-04-02 DOI: 10.1016/j.stem.2026.03.005

Verena J. Kast, Fatemeh Navaee, Majid Halvaei, Stefan Liebau, Ninel Azoitei, Markus Breunig, Peter Loskill, Alexander Kleger

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Rebuilding the bridge: Functional AVN cells for cardiac repair 重建桥：用于心脏修复的功能性AVN细胞