Cell stem cell最新文献

How ever-expanding organoids from epithelial stem cells were developed: A hypothesis-free approach. 上皮干细胞不断扩大的类器官是如何发展的：一种无假设的方法。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.001

Hans Clevers

引用次数: 0

Advancing hepatocyte-based therapies: A translational perspective. 推进肝细胞为基础的治疗：翻译的角度。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.007

Zhen Sun, Ludi Zhang, Lijian Hui

{"title":"Advancing hepatocyte-based therapies: A translational perspective.","authors":"Zhen Sun, Ludi Zhang, Lijian Hui","doi":"10.1016/j.stem.2026.04.007","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.007","url":null,"abstract":"Hepatocyte-based therapies represent a promising alternative to liver transplantation, yet their clinical translation is constrained by the limited availability of functional cells and inefficient engraftment. Here, we review progress in the field from a translational perspective, focusing on strategies to overcome these core challenges. We analyze emerging cell sources derived from stem cell technologies and assess their therapeutic potential. These translational efforts are organized around two clinical paradigms: hepatocyte replacement for long-term functional correction and temporary hepatocyte support for liver failure. Beyond hepatocytes, we also discuss preclinical and translational advances involving other liver cell types. To conclude, we outline critical gaps that need to be addressed for clinical translation, including scalable good manufacturing practice (GMP)-compliant manufacturing, efficient preconditioning regimens, long-term immune compatibility with non-invasive graft monitoring, and patient stratification for optimal clinical outcomes. We also discuss how hepatocyte-based therapies can complement gene/RNA therapies and xenotransplantation to broaden treatment options for liver diseases.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 5","pages":"726-746"},"PeriodicalIF":20.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857999","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

Tracking time and space: A new integrative approach in spatiotemporal transcriptomics. 跟踪时间和空间：时空转录组学的一种新的综合方法。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.009

Suijuan Zhong, Qian Wu, Xiaoqun Wang

引用次数: 0

CAR-A astrocytes for Alzheimer's: Promise and challenge. CAR-A星形胶质细胞治疗阿尔茨海默病：希望与挑战。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.008

Se-In Lee, Wenjie Luo, Li Gan

引用次数: 0

Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats. 胚胎MGE前体细胞移植到成年大鼠纹状体后，可整合并改善6-羟多巴胺损伤大鼠的运动症状。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 Epub Date: 2026-04-28 DOI: 10.1016/j.stem.2026.04.011

Verónica Martínez-Cerdeño, Stephen C Noctor, Ana Espinosa, Jeanelle Ariza, Philip Parker, Samantha Orasji, Marcel M Daadi, Krystof Bankiewicz, Arturo Alvarez-Buylla, Arnold R Kriegstein

引用次数: 0

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

Leukemic stem cell subtypes determine venetoclax resistance and therapeutic vulnerabilities in AML. 白血病干细胞亚型决定急性髓性白血病（AML）的venetoclax耐药性和治疗脆弱性。

IF 20.4

Cell stem cell Pub Date : 2026-05-07 DOI: 10.1016/j.stem.2026.04.012

Alexander Waclawiczek, Aino-Maija Leppä, Simon Renders, Ines Bergerweiss, Karolin Stumpf, Barbara Betz, Susanna Gabrowski, Frank Y Huang, Maria-Eleni Lalioti, Bendix Hempel, Markus Sohn, Heikki Kuusanmäki, Vera Thiel, Julia M Unglaub, Rabia Shahswar, Sarah Richter, Maike Janssen, Darja Karpova, Elisa Donato, Halvard Bonig, Christoph Röllig, Simon Raffel, Michael Heuser, Michael Hundemer, Mika Kontro, Ann-Kathrin Eisfeld, Tim Sauer, Nina Cabezas-Wallscheid, Carsten Müller-Tidow, Andreas Trumpp

{"title":"Leukemic stem cell subtypes determine venetoclax resistance and therapeutic vulnerabilities in AML.","authors":"Alexander Waclawiczek, Aino-Maija Leppä, Simon Renders, Ines Bergerweiss, Karolin Stumpf, Barbara Betz, Susanna Gabrowski, Frank Y Huang, Maria-Eleni Lalioti, Bendix Hempel, Markus Sohn, Heikki Kuusanmäki, Vera Thiel, Julia M Unglaub, Rabia Shahswar, Sarah Richter, Maike Janssen, Darja Karpova, Elisa Donato, Halvard Bonig, Christoph Röllig, Simon Raffel, Michael Heuser, Michael Hundemer, Mika Kontro, Ann-Kathrin Eisfeld, Tim Sauer, Nina Cabezas-Wallscheid, Carsten Müller-Tidow, Andreas Trumpp","doi":"10.1016/j.stem.2026.04.012","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.012","url":null,"abstract":"The BCL-2 inhibitor venetoclax has transformed the treatment of acute myeloid leukemia (AML), but relapse due to resistance of leukemic stem cells (LSCs) remains a major challenge. By molecular and functional profiling of LSCs from >150 patients, we identify four LSC subtypes. These mirror distinct hematopoietic lineage stages, which determine the expression ratio between the venetoclax target BCL-2 and resistance-inducing proteins MCL-1 and BCL-xL (MAC-score). Longitudinal analyses reveal that venetoclax resistance mostly arises in LSCs through plasticity toward a megakaryocytic/erythroid-progenitor (MEP)-LSC state that switches survival dependency from BCL-2 to BCL-xL. In rare cases, mature monocytic/dendritic (MoDe)-LSCs, found within LAMP5+ monocytic AMLs, drive venetoclax resistance. LSC subtyping improves genetic risk stratification and provides subtype-specific therapies: venetoclax-resistant MEP-LSCs respond to BCL-xL inhibitors, whereas MoDe-LSCs are sensitive to MEK1/2 inhibition. Our findings reveal four distinct LSC types with unique vulnerabilities and propose biomarker-guided treatment strategies that complement genetic profiling to overcome venetoclax resistance.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147858005","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

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

eIF4G2-mediated selective translation of chromatin regulators safeguards adult intestinal stem cell identity and differentiation. eif4g2介导的染色质调控因子的选择性翻译保护成体肠干细胞的身份和分化。

IF 20.4

Cell stem cell Pub Date : 2026-04-30 DOI: 10.1016/j.stem.2026.04.006

Haruko Kunitomi, Aye Myat Khaine, Radia Jamee, Vanessa Arreola, Mariselle Lancero, Amba Raychaudhuri, Samuel Perli, Yoshiko Sato, Mio Iwasaki, Pedro Ruivo, Kiichiro Tomoda, Mari Mito, Yuichi Shichino, Shintaro Iwasaki, Shinya Yamanaka

{"title":"eIF4G2-mediated selective translation of chromatin regulators safeguards adult intestinal stem cell identity and differentiation.","authors":"Haruko Kunitomi, Aye Myat Khaine, Radia Jamee, Vanessa Arreola, Mariselle Lancero, Amba Raychaudhuri, Samuel Perli, Yoshiko Sato, Mio Iwasaki, Pedro Ruivo, Kiichiro Tomoda, Mari Mito, Yuichi Shichino, Shintaro Iwasaki, Shinya Yamanaka","doi":"10.1016/j.stem.2026.04.006","DOIUrl":"https://doi.org/10.1016/j.stem.2026.04.006","url":null,"abstract":"eIF4G2 (DAP5/NAT1) is a non-canonical translation initiation factor, but its role in homeostasis is unclear. Using inducible Eif4g2 knockout mice and intestinal organoids, we show that eIF4G2 loss collapses Lgr5+ intestinal stem cell (ISC) and secretory maturation programs while preserving villus architecture. Transcriptomic and single-nucleus multiome analyses reveal a durable fetal-like/regenerative state with YAP-TEAD activation and regenerative absorptive cells. Ribosome profiling identifies selective translation-efficiency loss among chromatin regulators, especially the KAT3 coactivators CREBBP and EP300, resulting in reduced KAT3 abundance and global histone acetylation; chemical KAT3 inhibition phenocopies this state. CUT&Tag and assay for transposase-accessible chromatin sequencing (ATAC-seq) demonstrate that reduced eIF4G2-KAT3 output drives locus-selective enhancer remodeling, with loss of adult ISC/Wnt-Notch elements and activation of TEAD-enriched fetal loci, without inflammatory or integrated stress response programs driving the transition. Fetal intestinal spheroids remain viable despite similar biochemical defects, highlighting a stage-specific requirement for translational buffering in maintaining adult identity.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824702","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