Cell stem cell最新文献_第6页

From breakdown to repair: A human organoid model of menstruation. 从故障到修复：人类月经的类器官模型。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.010

Elisa T Zhang

引用次数: 0

An in vitro menstrual cycle using organoids captures epithelial cell transitions during menstruation and regeneration of the human endometrium. 使用类器官的体外月经周期捕获月经期间上皮细胞的转变和人子宫内膜的再生。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 Epub Date: 2026-04-28 DOI: 10.1016/j.stem.2026.04.005

Konstantina Nikolakopoulou, Weand Ybañez, Lhéanna Klaeylé, Lisa Frugoli, Tereza Cindrova-Davies, Hans-Rudolf Hotz, Charlotte Soneson, Margherita Yayoi Turco

{"title":"An in vitro menstrual cycle using organoids captures epithelial cell transitions during menstruation and regeneration of the human endometrium.","authors":"Konstantina Nikolakopoulou, Weand Ybañez, Lhéanna Klaeylé, Lisa Frugoli, Tereza Cindrova-Davies, Hans-Rudolf Hotz, Charlotte Soneson, Margherita Yayoi Turco","doi":"10.1016/j.stem.2026.04.005","DOIUrl":"10.1016/j.stem.2026.04.005","url":null,"abstract":"Menstruation is an unusual process in which the human endometrium undergoes cyclical shedding with scarless regeneration. Despite its pivotal role in reproductive health, the cellular states and interactions orchestrating this process remain poorly defined, largely due to the lack of in vitro systems that capture the inaccessible perimenstrual window. We use human endometrial organoids to establish an in vitro menstrual cycle (IVMC) protocol that recapitulates cyclical epithelial dynamics. We validate the IVMC by benchmarking against in vivo samples spanning the menstrual window through histology, transcriptomic, and multiplex secreted-protein analysis. During menstruation, the in vivo luminal epithelium acquires a distinct transcriptomic signature, characterized by WNT7A expression. Loss of WNT7A compromises long-term organoid survival, highlighting its functional importance. The regeneration-associated luminal epithelium acts as a signaling hub during regeneration through interactions with the vasculature. This work opens new avenues to dissect the unique regenerative program of the endometrium in health and disease.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"747-762.e8"},"PeriodicalIF":20.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Species-specific chromatin architecture and neurogenesis mediated by a human enhancer. 人类增强子介导的物种特异性染色质结构和神经发生。

IF 20.4

Cell stem cell Pub Date : 2026-04-02 Epub Date: 2026-03-19 DOI: 10.1016/j.stem.2026.02.009

Federica Mosti, Jing Liu, Katie Lam, Noah R Dillon, Samantha Skavicus, Victoria A Kapps, Ketrin Gjoni, Chia-Fang Lee, Emily N Glidewell, Nicholas S Heaton, Katherine S Pollard, Debra L Silver

{"title":"Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.","authors":"Federica Mosti, Jing Liu, Katie Lam, Noah R Dillon, Samantha Skavicus, Victoria A Kapps, Ketrin Gjoni, Chia-Fang Lee, Emily N Glidewell, Nicholas S Heaton, Katherine S Pollard, Debra L Silver","doi":"10.1016/j.stem.2026.02.009","DOIUrl":"10.1016/j.stem.2026.02.009","url":null,"abstract":"Genomic modifications underlie the evolution of human brain features, including a larger neocortex. Human accelerated regions (HARs) are highly conserved loci containing human-specific variants, with ∼50% identified as neurodevelopmental enhancers. However, the neurodevelopmental functions of HARs and their mechanisms of gene regulation are largely unknown. We show that human (Homo sapiens [Hs]) HAR1984 promotes neurogenesis by influencing species-specific transcription and chromatin interactions. Hs-HAR1984 knockin chimpanzee (Pan troglodytes [Pt]) cortical organoids contain more progenitors and neurons, whereas Pt-HAR1984 knockin human cortical organoids exhibit the opposite phenotype. Hs-HAR1984 knockin mice have increased neurogenesis and a thicker cortex with focal folds. HAR1984 exhibits chromatin looping with its target genes, ETV5 and TRA2B, in human fetal brains, which is notably reduced in chimpanzee, macaque, and mouse neural cells. We show that human-specific HAR1984 promotes these interactions and that human-specific ETS variant transcription factor 5 (ETV5) binding auto-regulates enhancer activity. Our study demonstrates molecular mechanisms underlying human-specific neurodevelopment, linking HARs to chromatin architecture, cortical fate, and expansion.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"695-714.e10"},"PeriodicalIF":20.4,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered intestinal crypt geometry uncovers YAP1-dependent fetal-to-adult transition. 工程肠隐窝几何揭示了依赖yap1的胎儿到成人的转变。

IF 20.4

Cell stem cell Pub Date : 2026-03-05 Epub Date: 2026-02-12 DOI: 10.1016/j.stem.2026.01.006

Martti Maimets, Mikhail Nikolaev, Cecilia Lövkvist, Fabien Bertillot, Hjalte List Larsen, Raul Bardini Bressan, Antonios Georgantzoglou, Nikolce Gjorevski, Eirini Filidou, Maureen Zøylner, Stine Lind Hansen, Astrid M Baattrup, Isidora Banjac, Jordi Guiu, Sara A Wickström, Matthias P Lutolf, Kim B Jensen

{"title":"Engineered intestinal crypt geometry uncovers YAP1-dependent fetal-to-adult transition.","authors":"Martti Maimets, Mikhail Nikolaev, Cecilia Lövkvist, Fabien Bertillot, Hjalte List Larsen, Raul Bardini Bressan, Antonios Georgantzoglou, Nikolce Gjorevski, Eirini Filidou, Maureen Zøylner, Stine Lind Hansen, Astrid M Baattrup, Isidora Banjac, Jordi Guiu, Sara A Wickström, Matthias P Lutolf, Kim B Jensen","doi":"10.1016/j.stem.2026.01.006","DOIUrl":"10.1016/j.stem.2026.01.006","url":null,"abstract":"During morphogenesis, the intestine undergoes significant structural remodeling, transitioning from a simple tube of immature epithelium into a complex crypt-villus architecture housing mature cell types. However, the relationship between these structural changes and epithelial maturation has remained enigmatic. Using engineered scaffolds that replicate crypt-like geometries, we establish a robust platform for guiding the morphogenesis and differentiation of fetal intestinal cells into mature engineered tissues that mimic their in vivo counterparts. Mechanistically, tissue maturation is driven by cell crowding, leading to reduced YAP1 activation. Modulating YAP signaling in both engineered tissues and the developing mouse intestine alters epithelial lineage specification. These findings uncover a geometry-dependent mechanism that links tissue architecture to cell fate transitions. Our work provides a platform for modeling aspects of intestinal development and offers insights for refining stem cell differentiation protocols and regenerative strategies for intestinal disorders.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"487-501.e7"},"PeriodicalIF":20.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency. 化学诱导多能性过程中的染色质接近动力学。

IF 20.4

Cell stem cell Pub Date : 2026-03-05 Epub Date: 2026-02-05 DOI: 10.1016/j.stem.2026.01.011

Shangtao Cao, Shengyong Yu, Dongwei Li, Jing Ye, Xuejie Yang, Chen Li, Xiaoshan Wang, Yuanbang Mai, Yue Qin, Jian Wu, Jiangping He, Chunhua Zhou, He Liu, Bentian Zhao, Xiaodong Shu, Chuman Wu, Ruiping Chen, Waiyee Chan, Guangjin Pan, Jiekai Chen, Jing Liu, Duanqing Pei

引用次数: 0

Prevention of transgene silencing during human pluripotent stem cell differentiation. 人类多能干细胞分化过程中转基因沉默的预防。

IF 20.4

Cell stem cell Pub Date : 2026-03-05 Epub Date: 2026-02-13 DOI: 10.1016/j.stem.2026.01.007

Takeshi Uenaka, Alan Napole, Aninda Dibya Saha, Duo Sun, Angelina Singavarapu, Elizabeth Calzada, Jiahui Chen, Lena Erlebach, Amanda McQuade, Daniel M Ramos, Alessandra Rigamonti, Lisa Salazar, Avi J Samelson, Kamilla Sedov, Natalie J Welsh, Katleen Wild, Qianxin Wu, Ernest Arenas, Andrew R Bassett, Martin Kampmann, Deborah Kronenberg-Versteeg, Florian T Merkle, Birgitt Schüle, Leslie M Thompson, William C Skarnes, Michael E Ward, Marius Wernig

{"title":"Prevention of transgene silencing during human pluripotent stem cell differentiation.","authors":"Takeshi Uenaka, Alan Napole, Aninda Dibya Saha, Duo Sun, Angelina Singavarapu, Elizabeth Calzada, Jiahui Chen, Lena Erlebach, Amanda McQuade, Daniel M Ramos, Alessandra Rigamonti, Lisa Salazar, Avi J Samelson, Kamilla Sedov, Natalie J Welsh, Katleen Wild, Qianxin Wu, Ernest Arenas, Andrew R Bassett, Martin Kampmann, Deborah Kronenberg-Versteeg, Florian T Merkle, Birgitt Schüle, Leslie M Thompson, William C Skarnes, Michael E Ward, Marius Wernig","doi":"10.1016/j.stem.2026.01.007","DOIUrl":"10.1016/j.stem.2026.01.007","url":null,"abstract":"Transgenes are often silenced upon differentiation of pluripotent stem cells using conventional expression systems. Here, we developed the TK4 PiggyBac vector to conduct a comparative analysis to evaluate the impact of various promoters, transcriptional regulatory elements, insulators, and genomic integration sites on transgene silencing during neuronal differentiation. Our findings reveal that specific combinations of CAG and Ubc promoters with the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) can prevent transgene silencing during differentiation, whereas chromatin insulators have less impact on sustained expression. Three novel safe harbor loci, distant from known genes, as well as the citrate lyase beta-like (CLYBL) locus, similarly support the prevention of transgene silencing. Remarkably, the TK4 vector showed complete resistance to silencing across various neuronal and microglial differentiation protocols, as independently confirmed by seven laboratories. This construct will be highly useful for assays requiring stable transgene expression during differentiation and holds potential for broad applications in various research fields.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"517-530.e8"},"PeriodicalIF":20.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 3D "nichoid" boost for gene-engineered blood stem cells. 基因工程造血干细胞的3D“nichoid”增强。

IF 20.4

Cell stem cell Pub Date : 2026-02-05 DOI: 10.1016/j.stem.2026.01.004

Giulia Schiroli, Pietro Genovese

引用次数: 0

Sleep disturbance triggers aberrant activation of vagus circuitry and induces intestinal stem cell dysfunction. 睡眠障碍引发迷走神经回路异常激活，诱发肠道干细胞功能障碍。

IF 20.4

Cell stem cell Pub Date : 2026-02-05 DOI: 10.1016/j.stem.2026.01.002

Mingxin Zhang, Xi Wu, Di Liu, Huaxing Li, Xulin Li, Wuqi Yang, Jialin Ye, Liyuan Hou, Shiyang Wang, Ning Ning, Hanfu Zhang, Yuhua Tian, Lu Yu, Kaichun Wu, Liping Wang, Maksim V Plikus, Cong Lv, Feng Wang, Zhengquan Yu

{"title":"Sleep disturbance triggers aberrant activation of vagus circuitry and induces intestinal stem cell dysfunction.","authors":"Mingxin Zhang, Xi Wu, Di Liu, Huaxing Li, Xulin Li, Wuqi Yang, Jialin Ye, Liyuan Hou, Shiyang Wang, Ning Ning, Hanfu Zhang, Yuhua Tian, Lu Yu, Kaichun Wu, Liping Wang, Maksim V Plikus, Cong Lv, Feng Wang, Zhengquan Yu","doi":"10.1016/j.stem.2026.01.002","DOIUrl":"10.1016/j.stem.2026.01.002","url":null,"abstract":"Sleep disturbances are associated with pathogenesis of numerous chronic disorders, including chronic gastrointestinal diseases. However, the mechanism that transmits sleep disturbance-induced aberrant neural signaling from the brain to the gut remains elusive. We show that acute sleep deprivation (SD) impairs intestinal stem cell (ISC) function, leading to shortening of crypt-villus architecture and Paneth cell loss. We identified the dorsal motor nucleus of vagus (DMV) as the SD-sensitive central nervous system center that transmits sleep effects to the gut. SD aberrantly activates DMV neurons, driving excessive acetylcholine release from the vagus nerve into the gut. Acetylcholine triggers 5-hydroxytryptamine (5-HT) release by enterochromaffin cells and suppresses its reuptake via muscarinic receptors, thereby causing a spike in 5-HT levels. Elevated 5-HT induces excessive oxidative stress in ISCs through its receptor HTR4, promoting gut pathologies. Overall, we reveal an SD-responsive neural circuit that controls ISCs and identify therapeutic strategies for mitigating SD-related gut diseases.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 2","pages":"306-324.e8"},"PeriodicalIF":20.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nurturing eggs with hiPSC-derived cells to improve outcomes in in vitro fertilization. 用hipsc来源的细胞培养卵子以改善体外受精的结果。

IF 20.4

Cell stem cell Pub Date : 2026-02-05 DOI: 10.1016/j.stem.2026.01.005

Fang Fang, Renee A Reijo Pera

引用次数: 0

Editing the skin in place: In vivo genome correction of rare skin disease. 就地编辑皮肤：罕见皮肤病的体内基因组校正。

IF 20.4

Cell stem cell Pub Date : 2026-02-05 DOI: 10.1016/j.stem.2026.01.003

Rohan Palanki, Emily Fitzgerald, Alexandre J Poirier, Michael J Mitchell

引用次数: 0