Cell stem cell最新文献

Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury 细菌adp -庚糖触发肠上皮损伤后干细胞再生

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-11 DOI: 10.1016/j.stem.2025.06.009

Shawn Goyal, Cynthia X. Guo, Ojas Singh, Adrienne Ranger, Caitlin F. Harrigan, Justin Meade, Alexander Luchak, Derek K. Tsang, Herbert Y. Gaisano, Nan Gao, Scott A. Yuzwa, Jeffrey L. Wrana, Dana J. Philpott, Scott D. Gray-Owen, Stephen E. Girardin

{"title":"Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury","authors":"Shawn Goyal, Cynthia X. Guo, Ojas Singh, Adrienne Ranger, Caitlin F. Harrigan, Justin Meade, Alexander Luchak, Derek K. Tsang, Herbert Y. Gaisano, Nan Gao, Scott A. Yuzwa, Jeffrey L. Wrana, Dana J. Philpott, Scott D. Gray-Owen, Stephen E. Girardin","doi":"10.1016/j.stem.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.06.009","url":null,"abstract":"ADP-heptose (ADP-Hep), a metabolite produced by gram-negative bacteria, is detected in the host cytosol by the kinase ALPK1, which engages TIFA-dependent innate immune responses. However, the function of ALPK1-TIFA signaling in primary cells and in physiological settings remains poorly understood. Here, we showed that, in the intestinal epithelium, ALPK1 and TIFA were mainly expressed by the intestinal stem cell (ISC) pool, where they controlled the replacement of homeostatic ISCs by new revival stem cells (revSCs) following injury. Mechanistically, ADP-Hep triggered pro-inflammatory nuclear factor κB (NF-κB) signaling and tumor necrosis factor (TNF)-dependent ISC apoptosis, which initiated a transforming growth factor β (TGF-β)- and YAP-dependent revSC program. Single-cell transcriptomics and lineage-tracing experiments identified Paneth cells as a cell of origin for revSC induction in response to ADP-Hep. In vivo, revSC emergence following irradiation or dextran-sodium-sulfate-induced injury was blunted in Tifa−/− mice. Together, our work reveals that ALPK1-TIFA signaling contributes to ISC turnover in response to bacterial detection in the intestine.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"21 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602853","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

From symbiote to bad neighbor: The intestinal microbiome as a driver of CHIP 从共生体到坏邻居：肠道微生物组作为CHIP的驱动因素

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-03 DOI: 10.1016/j.stem.2025.06.003

Courtney M. Cowan, Eric M. Pietras

引用次数: 0

Beyond transplantation: Gene-edited pig liver supports function in a human host 超越移植：基因编辑的猪肝支持人类宿主的功能

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-03 DOI: 10.1016/j.stem.2025.06.005

Hidetaka Hara, Yi Wang

引用次数: 0

Toward building kidney organoids with plumbing: Fusion of nephron with ureteric bud 构建有管道的类肾器官：肾元与输尿管芽的融合

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-03 DOI: 10.1016/j.stem.2025.06.001

Chao Zhang, Yun Xia

引用次数: 0

The future belongs to those who believe in multiplex CAR T engineering 未来属于那些相信多重CAR - T工程的人

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-03 DOI: 10.1016/j.stem.2025.06.008

Laura Volta, Chiara F. Magnani

引用次数: 0

TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice tet2突变骨髓细胞通过中枢神经系统浸润和增强吞噬作用减轻小鼠阿尔茨海默病的进展

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-07-02 DOI: 10.1016/j.stem.2025.06.006

Katie A. Matatall, Trisha K. Wathan, Minh Nguyen, Hu Chen, Alexandra McDonald, Guantong Qi, Julia A. Belk, Marcus A. Florez, Duy T. Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M. Buttigieg, Chih-wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E. Kennedy, Arushana A. Maknojia, Apoorva Thatavarty, Josaura V. Fernandez Sanchez, Hind Bouzid, Katherine Y. King

{"title":"TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice","authors":"Katie A. Matatall, Trisha K. Wathan, Minh Nguyen, Hu Chen, Alexandra McDonald, Guantong Qi, Julia A. Belk, Marcus A. Florez, Duy T. Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M. Buttigieg, Chih-wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E. Kennedy, Arushana A. Maknojia, Apoorva Thatavarty, Josaura V. Fernandez Sanchez, Hind Bouzid, Katherine Y. King","doi":"10.1016/j.stem.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.06.006","url":null,"abstract":"Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer’s disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than DNMT3A-mutant or wild-type microglia. Strikingly, single-cell RNA sequencing (scRNA-seq) revealed that macrophages and patrolling monocytes were increased in brains of mice transplanted with Tet2-mutant marrow in response to chemokine signaling. These studies reveal a TET2-specific protective effect of CH on AD pathogenesis mediated by peripheral myeloid cell infiltration.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"3 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533906","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

Hallmarks of stem cell aging 干细胞老化的特征

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-24 DOI: 10.1016/j.stem.2025.06.004

Thomas A. Rando, Anne Brunet, Margaret A. Goodell

引用次数: 0

An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier 利用ipsc衍生的脊髓运动神经元和一体化血脑样屏障建立散发性ALS器官芯片模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-24 DOI: 10.1016/j.stem.2025.05.015

Deepti Lall, Michael J. Workman, Samuel Sances, Briana N. Ondatje, Shaughn Bell, George Lawless, Amanda Woodbury, Dylan West, Amanda Meyer, Andrea Matlock, Vineet Vaibhav, Jennifer E. Van Eyk, Clive N. Svendsen

{"title":"An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier","authors":"Deepti Lall, Michael J. Workman, Samuel Sances, Briana N. Ondatje, Shaughn Bell, George Lawless, Amanda Woodbury, Dylan West, Amanda Meyer, Andrea Matlock, Vineet Vaibhav, Jennifer E. Van Eyk, Clive N. Svendsen","doi":"10.1016/j.stem.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.015","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder in which motor neurons (MNs) of the brain and spinal cord degenerate, leading to paralysis. Generating MNs from patient-specific induced pluripotent stem cells (iPSCs) may help elucidate early stages of disease. Here, we combined MNs from patients with early-onset disease with brain microvascular endothelial-like cells in a microfluidic device we termed spinal cord chips (SC-chips) and added media flow, which enhanced neuronal maturation and improved cellular health. Bulk transcriptomic and proteomic analyses of SC-chips revealed differences between control and ALS samples, including increased levels of neurofilaments. Single-nuclei RNA sequencing revealed the presence of two MN subpopulations and an ALS-specific dysregulation of glutamatergic and synaptic signaling. This ALS SC-chip model generates a diversity of mature MNs to better understand ALS pathology in a model that has an active blood-brain barrier-like system for future drug screening.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"27 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370930","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

ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation ChemPerturb-seq筛选确定了一种小分子鸡尾酒，可提高人皮下移植后β细胞的存活率

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-24 DOI: 10.1016/j.stem.2025.06.002

J. Jeya Vandana, Jiajun Zhu, Alice Maria Giani, Tuo Zhang, Lauretta A. Lacko, Dongliang Leng, D. Leland Taylor, Brian N. Lee, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Xinyi Liu, Angie Chi Nok Chong, Dongxiang Xue, Zihe Meng, Jenny Z. Xiang, Chendong Pan, Wei Wang, Ali Naji, Shuibing Chen

{"title":"ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation","authors":"J. Jeya Vandana, Jiajun Zhu, Alice Maria Giani, Tuo Zhang, Lauretta A. Lacko, Dongliang Leng, D. Leland Taylor, Brian N. Lee, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Xinyi Liu, Angie Chi Nok Chong, Dongxiang Xue, Zihe Meng, Jenny Z. Xiang, Chendong Pan, Wei Wang, Ali Naji, Shuibing Chen","doi":"10.1016/j.stem.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.06.002","url":null,"abstract":"Traditional chemical screens have focused on a single assay per screen, making them labor intensive and costly. Here, we combined a chemical screen with single-cell RNA sequencing (scRNA-seq) to perform Chemical Perturb-seq (ChemPerturb-seq), enabling a systematic analysis of the molecular changes of human beta cells upon individual small molecule treatments. Using this platform, we performed an in vivo barcoded screen and discovered a small molecule cocktail, including beta-lipotropin 61-91, insulin growth factor-1, and prostaglandin E2, with which preconditioning human beta cells and primary islets significantly enhanced function and survival when transplanted subcutaneously to female, but not to male, mice. We identified two additional molecules, serotonin and histamine, that promote islet function when transplanted subcutaneously to male mice using ChemPerturb-seq. Such small molecule cocktails could be applied to improve the current FDA-approved islet transplantation procedure. Finally, we developed an artificial intelligence (AI)-powered website, ChemPerturbDB, which provides user-friendly open access analysis of the extensive ChemPerturb-seq dataset.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"26 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371170","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

To play Paneth or goblet: Shapeshifting secretory cells read the room 玩潘尼斯或高脚杯：变形分泌细胞读取房间

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-18 DOI: 10.1016/j.stem.2025.06.007

Irene V. Choi, Rachel K. Zwick

引用次数: 0