Cell stem cell最新文献

EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogramming. EZHIP限制非规范PRC2结合，调控H3K27me3代际遗传和重编程。

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-20 DOI: 10.1016/j.stem.2025.09.009

Yitian Zeng,Feng Kong,Zihan Xu,Xukun Lu,Qian Li,Bofeng Liu,Shu Liu,Lijun Dong,Ling Liu,Wenying Wang,Bing Zhu,Wei Xie

{"title":"EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogramming.","authors":"Yitian Zeng,Feng Kong,Zihan Xu,Xukun Lu,Qian Li,Bofeng Liu,Shu Liu,Lijun Dong,Ling Liu,Wenying Wang,Bing Zhu,Wei Xie","doi":"10.1016/j.stem.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.09.009","url":null,"abstract":"In mice, the repressive histone mark H3K27me3 undergoes both region-specific inheritance and erasure during the parental-to-embryonic transition, with the underlying mechanisms poorly understood. Here, we show that PRC2, which catalyzes H3K27me3, binds both classic Polycomb targets and noncanonical H3K27me3 domains in growing oocytes but dissociates from chromatin in fully grown oocytes. After fertilization, PRC2 rebinds noncanonical H3K27me3 domains before relocating to Polycomb targets in blastocysts. Interestingly, the binding and activity of PRC2 are restricted by a maternal inhibitory factor, EZH inhibitory protein (EZHIP), which co-binds with PRC2. Upon knockout of Ezhip, hyperactive PRC2 promiscuously deposits H3K27me3 genome-wide. This overwrites H3K27me3 memories at noncanonical imprinted genes and paradoxically causes derepression of H3K27me3 targets, defective X chromosome inactivation, and diluted chromatin PRC2. H3K27me3 restoration at Polycomb targets after implantation is also attenuated, accompanied by sub-lethality. These data unveil principles of epigenetic inheritance that both insufficient and excessive heterochromatic marks cause loss of epigenetic memories and repression.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"25 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338563","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

Vitamin C conveys geroprotection on primate ovaries 维生素C对灵长类动物的卵巢具有衰老保护作用

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-14 DOI: 10.1016/j.stem.2025.09.008

Ying Jing, Huifen Lu, Jingyi Li, Zan He, Liyun Zhao, Chen Zhang, Ziqi Huang, Lixiao Liu, Shuhui Sun, Shuai Ma, Concepcion Rodriguez Esteban, Xiaobing Fu, Guoguang Zhao, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Si Wang, Guang-Hui Liu

引用次数: 0

Crosstalk between tissue mechanics and BMP4 signaling regulates symmetry breaking in human gastrula models 组织力学和BMP4信号之间的串扰调节人原肠模型中的对称性破坏

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-13 DOI: 10.1016/j.stem.2025.09.006

Riccardo De Santis, Laurent Jutras-Dubé, Sophia Bourdrel, Eleni Rice, Francesco M. Piccolo, Ali H. Brivanlou

{"title":"Crosstalk between tissue mechanics and BMP4 signaling regulates symmetry breaking in human gastrula models","authors":"Riccardo De Santis, Laurent Jutras-Dubé, Sophia Bourdrel, Eleni Rice, Francesco M. Piccolo, Ali H. Brivanlou","doi":"10.1016/j.stem.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.09.006","url":null,"abstract":"The spatiotemporal regulation of morphogenetic signals, along with local tissue mechanics, guides morphogenesis and determines the shape of the embryo. However, how these signals integrate into developmental circuits remains poorly understood. Here, we developed a light-inducible strategy to induce BMP4 signaling with precise spatial coordinates in human pluripotent stem cells. Light-controlled BMP4 induces SMAD1–5 phosphorylation, resulting in amnion differentiation, and relies on a tension-dependent induction of WNT and NODAL for mesoderm differentiation. In response to BMP4 signaling, the mechanosensitive transcription factor YAP1 accumulates in the nucleus, where it represses WNT3 mRNA, regulating the induction of the three germ layers. Based on these findings, we developed a mathematical model that integrates tissue mechanics into morphogen dynamics, quantitatively explaining tissue-scale responses to BMP4 signaling. Thus, light induction of the morphogen BMP4 in human stem cell models elucidated the interplay between tissue mechanics and signaling at the onset of gastrulation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283472","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

Hypoxia promotes airway differentiation in the human lung epithelium 缺氧促进人肺上皮的气道分化

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-10 DOI: 10.1016/j.stem.2025.09.007

Ziqi Dong, Niek Wit, Aastha Agarwal, Adam James Reid, Dnyanesh Dubal, Sina Beier, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Jelle van den Ameele, James A. Nathan, Emma L. Rawlins

{"title":"Hypoxia promotes airway differentiation in the human lung epithelium","authors":"Ziqi Dong, Niek Wit, Aastha Agarwal, Adam James Reid, Dnyanesh Dubal, Sina Beier, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Jelle van den Ameele, James A. Nathan, Emma L. Rawlins","doi":"10.1016/j.stem.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.09.007","url":null,"abstract":"Human lungs experience dynamic oxygen tension during development. Here, we show that hypoxia directly regulates human lung epithelial cell identity using tissue-derived organoids. Fetal multipotent lung epithelial progenitors remain undifferentiated in a self-renewing culture condition under normoxia but spontaneously differentiate toward multiple airway cell types and inhibit alveolar differentiation under hypoxia. Using chemical and genetic tools, we demonstrate that hypoxia-induced airway differentiation depends on hypoxia-inducible factor (HIF) activity, with HIF1α and HIF2α differentially regulating progenitor fate decisions. KLF4 and KLF5 are direct HIF targets that promote basal and secretory cell fates. Moreover, hypoxia is sufficient to convert alveolar type 2 cells derived from both human fetal and adult lungs to airway cells, including aberrant basal-like cells that exist in human fibrotic lungs. These findings reveal roles for hypoxia and HIF activity in the developing human lung epithelium and have implications for aberrant cell fate changes in pathological lungs.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"109 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255050","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

Unmasking cancer’s hidden nerve route with patient-derived organoids 用病人来源的类器官揭示癌症隐藏的神经通路

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-02 DOI: 10.1016/j.stem.2025.08.008

Kevin M. Waters, Akil Merchant, De-Chen Lin

引用次数: 0

Mind, mood and new neurons: Probing adult hippocampal neurogenesis in neuropsychiatry and beyond 心智、情绪和新神经元：在神经精神病学及其他领域探索成人海马神经发生

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-10-02 DOI: 10.1016/j.stem.2025.09.005

Giorgia Tosoni, Evgenia Salta

引用次数: 0

Stem cell research in space: Advancing regenerative medicine beyond Earth 太空中的干细胞研究：在地球之外推进再生医学