Cell stem cell最新文献_第5页

Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging. 海马神经前体细胞对铁下垂的敏感性影响神经发生和记忆。

IF 20.4

Cell stem cell Pub Date : 2026-06-04 Epub Date: 2026-05-22 DOI: 10.1016/j.stem.2026.04.017

Zhenyu Zhang, Alison K Carlisle, Hamish P Carter, Joshua R Lowe, Menekse Mutlu-Smith, Wendy Lee, Odette Leiter, Shilong Zhang, Annie Harding, Muhammed Syed, David Brici, Rupert W Overall, Nicole Rund, Christina Steinhauer, Daniel G Blackmore, Scott Ayton, Ashley I Bush, Ming Chen, Gerd Kempermann, Sheng-Tao Hou, Tara L Walker

{"title":"Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging.","authors":"Zhenyu Zhang, Alison K Carlisle, Hamish P Carter, Joshua R Lowe, Menekse Mutlu-Smith, Wendy Lee, Odette Leiter, Shilong Zhang, Annie Harding, Muhammed Syed, David Brici, Rupert W Overall, Nicole Rund, Christina Steinhauer, Daniel G Blackmore, Scott Ayton, Ashley I Bush, Ming Chen, Gerd Kempermann, Sheng-Tao Hou, Tara L Walker","doi":"10.1016/j.stem.2026.04.017","DOIUrl":"10.1016/j.stem.2026.04.017","url":null,"abstract":"Adult hippocampal neurogenesis declines with age, but the stress pathways that shape neural precursor cell (NPC) survival and lineage progression remain incompletely understood. Here, we tested whether ferroptosis-related vulnerability contributes to the regulation of hippocampal NPCs and their progeny. Using in vitro assays, transcriptomic analyses, and in vivo genetic and pharmacologic perturbations, we find that NPCs show features consistent with elevated susceptibility to ferroptotic stress relative to more differentiated hippocampal populations. Reducing glutathione peroxidase 4 (GPX4) or increasing ferroptotic stress impairs neurogenesis-associated cellular and behavioral phenotypes, whereas pathway modulation improves selected outcomes in aged animals. These effects were context dependent, with distinct consequences across age and behavioral paradigms. Together, the findings support a model in which ferroptosis-related susceptibility contributes to the regulation of adult hippocampal neurogenesis and cognition.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1031-1046.e8"},"PeriodicalIF":20.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007750","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

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 : 2026-06-04 Epub 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":"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":"982-999.e8"},"PeriodicalIF":20.4,"publicationDate":"2026-06-04","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

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 : 2026-06-04 Epub 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":"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":"1000-1015.e11"},"PeriodicalIF":20.4,"publicationDate":"2026-06-04","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

A precision product framework for context-dependent mechanisms of MSC therapy. MSC治疗的上下文依赖机制的精确产品框架。

IF 20.4

Cell stem cell Pub Date : 2026-06-04 Epub Date: 2026-05-21 DOI: 10.1016/j.stem.2026.04.015

Donald G Phinney

{"title":"A precision product framework for context-dependent mechanisms of MSC therapy.","authors":"Donald G Phinney","doi":"10.1016/j.stem.2026.04.015","DOIUrl":"10.1016/j.stem.2026.04.015","url":null,"abstract":"Despite decades of research, mesenchymal stem/stromal cell (MSC) therapy development has fallen short of expectations. Although regulatory convention prioritizes viability-centric metrics as proxies for potency, emerging evidence indicates that, in specific inflammatory contexts, efficacy is driven by apoptotic MSCs undergoing host efferocytosis. This paradox calls into question key assumptions underlying the \"living-drug\" paradigm. Here, I propose a \"precision product\" framework to resolve this dichotomy. By integrating conflicting data on cryopreservation, apoptosis, and metabolic activity, I discuss how paracrine signaling and apoptosis represent different phases of a functional continuum. Efficacy is not intrinsic to viability alone but depends on matching the product's state (secretory versus apoptotic) to the host's specific disease microenvironment. Ultimately, by abandoning reductionist \"one-size-fits-all\" manufacturing in favor of a precision product framework that embraces product heterogeneity and matches specific mechanisms of action to distinct disease microenvironments, the field can overcome current translational bottlenecks and more fully realize the therapeutic potential of MSC therapies.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"907-912"},"PeriodicalIF":20.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990484","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

Closing the gap: Toward functional, bioengineered esophageal grafts. 缩小差距：走向功能性生物工程食管移植物。

IF 20.4

Cell stem cell Pub Date : 2026-06-04 DOI: 10.1016/j.stem.2026.04.019

Dominique D Bailey, Jianwen Que

引用次数: 0

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":"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