Cell stem cellPub Date : 2026-03-23DOI: 10.1016/j.stem.2026.02.010
Zhongqiu Li, Yanxin Li, Ziqing He, Changliang Wang, Yuehong Zhang, Rong Li, Lei Jin, Jin Jiao, Fen Ji, Bing Zhu, Jingjing Zhang, Peng Du, Ji Dong, Jianwei Jiao
{"title":"Decoding the spatiotemporal development of the blood-brain barrier in human cortex","authors":"Zhongqiu Li, Yanxin Li, Ziqing He, Changliang Wang, Yuehong Zhang, Rong Li, Lei Jin, Jin Jiao, Fen Ji, Bing Zhu, Jingjing Zhang, Peng Du, Ji Dong, Jianwei Jiao","doi":"10.1016/j.stem.2026.02.010","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.010","url":null,"abstract":"","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501751","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}
{"title":"Auditory activity sustains adult neurogenesis and cognition through the locus coeruleus-norepinephrine system.","authors":"Qiang Liu,Xing Luo,Ziqi Liang,Dezhe Qin,Min Wang,Weixiang Guo","doi":"10.1016/j.stem.2026.02.008","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.008","url":null,"abstract":"Hearing loss has been considered as potentially the leading modifiable risk factor for cognitive decline and dementia, but the causal link between these two conditions remains unsolved. Here, we report that mice with specific ablation of cochlear outer hair cells display marked hearing loss, which in turn leads to cognitive impairment and defective adult hippocampal neurogenesis. Furthermore, we discover that the dentate gyrus receives auditory input through a neuraxis, which originates from glutamatergic neurons of the caudal pontine reticular nucleus (PnCvGluT2) and relays via norepinephrinergic neurons of the locus coeruleus (LCNEergic). Hearing loss diminishes PnCvGluT2 to LCNEergic neuronal afferents, thereby reducing norepinephrine levels. Notably, stimulating PnCvGluT2 to LCNEergic neuronal afferents rescues the defective neurogenesis and cognitive impairment caused by hearing loss. Therefore, our study establishes a causal relationship between hearing loss and cognitive decline and emphasizes the importance of hearing wellness in sustaining cognitive function.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"32 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490063","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}
{"title":"In vivo CAR-Tfh cell reprogramming restores tolerance in a mouse model of autoimmune hepatitis","authors":"Zuolin Zheng, Ying Liu, Ganyu Wang, Xinyuan Li, Shengxuan Peng, Zhen Jia, Xiao Yue, Zhipeng Fu, Xiaotian Zhao, Maosen Han, Zhenmei Yang, Chunwei Tang, Jinxin Gao, Zhichao Kong, Chen Chen, Kun Zhao, Tao Li, Xinyi Jiang, Weiqiang Jing","doi":"10.1016/j.stem.2026.02.006","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.006","url":null,"abstract":"Autoimmune diseases involve the coordinated dysregulation of multiple types of immune cells, and single-cell targeted therapies often yield suboptimal results. Here, we developed chimeric antigen receptor (CAR)-engineered follicular helper T (Tfh) cells capable of simultaneously suppressing T cells, B cells, and dendritic cells (DCs) to restore immune homeostasis in an autoimmune hepatitis (AIH) mouse model. Using amino acid-derived lipid nanoparticles, we deliver self-amplifying RNA encoding Forkhead box protein P3 (Foxp3) and a cytochrome P4502D6 (CYP2D6)-specific CAR to Tfh cells, conferring stable regulatory features and antigen-dependent suppressive activity. Engineered CAR-Tfh cells preferentially localize to the liver, recognize CYP2D6-expressing hepatocytes, and suppress pathogenic T cell and B cell responses. In AIH-II mouse models, CAR-Tfh cell generation restores a tolerogenic hepatic immune environment and ameliorates autoimmune liver injury. These findings establish <em>in situ</em> Tfh cell reprogramming as a modular approach to coordinately modulate multiple immune compartments, providing a potential therapeutic framework for AIH and related autoimmune diseases.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439684","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}
Cell stem cellPub Date : 2026-03-05DOI: 10.1016/j.stem.2026.02.002
Michinori Mayama,Eoin C Whelan,Takeshi Sato,David G Stouffer,Adrian N Leu,Jerome F Strauss,Richard J Auchus,Kotaro Sasaki
{"title":"Modeling human prenatal adrenocortical functional zonation dynamics from pluripotent stem cells.","authors":"Michinori Mayama,Eoin C Whelan,Takeshi Sato,David G Stouffer,Adrian N Leu,Jerome F Strauss,Richard J Auchus,Kotaro Sasaki","doi":"10.1016/j.stem.2026.02.002","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.002","url":null,"abstract":"The adrenal cortex produces essential steroid hormones through a concentric zonal architecture, established by the centripetal transdifferentiation of subcapsular progenitors within a capsule-derived niche. To capture this complexity, we establish a human pluripotent stem cell-derived adrenal organoid system that faithfully recapitulates this process. RSPO3/WNT signaling from the capsule specifies definitive zone (DZ) progenitors from the adrenal primordium, which then differentiate into a cortisol-producing transitional zone and an androgen-producing fetal zone under the influence of RSPO3 and ACTH. Loss of NR0B1 impairs DZ specification and triggers direct adrenal primordium-to-fetal zone conversion, mirroring the mechanism of X-linked adrenal hypoplasia congenita. When DZ cells are encapsulated with capsule cells separately derived from pluripotent stem cells, they reconstitute zonation in vivo, forming ACTH-responsive tissue that produces both cortisol and androgens. This organoid platform offers a powerful tool to dissect human adrenal development and establishes a foundation for regenerative therapies targeting adrenal diseases.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"56 1","pages":"454-469.e9"},"PeriodicalIF":23.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371019","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}
Cell stem cellPub Date : 2026-03-05DOI: 10.1016/j.stem.2026.01.014
Birte Doludda,Warsha Barde,Francesco D'Egidio,Carlos P Fitzsimons,Jonas Frisén,Fred H Gage,Sebastian Jessberger,Orly Lazarov,D Chichung Lie,Paul J Lucassen,Chiara de Lucia,Evgenia Salta,Hongjun Song,Juan Song,Sandrine Thuret,Tomohisa Toda,Gerd Kempermann
{"title":"Adult neurogenesis: New neurons, new opportunities.","authors":"Birte Doludda,Warsha Barde,Francesco D'Egidio,Carlos P Fitzsimons,Jonas Frisén,Fred H Gage,Sebastian Jessberger,Orly Lazarov,D Chichung Lie,Paul J Lucassen,Chiara de Lucia,Evgenia Salta,Hongjun Song,Juan Song,Sandrine Thuret,Tomohisa Toda,Gerd Kempermann","doi":"10.1016/j.stem.2026.01.014","DOIUrl":"https://doi.org/10.1016/j.stem.2026.01.014","url":null,"abstract":"The 38 currently registered clinical trials with the keyword \"adult neurogenesis\" indicate growing interest in new neurons as a target for intervention. Today, we have strong evidence that adult neurogenesis is involved in hippocampal function and can contribute to brain functions in health and disease. Neurogenesis research can now ask new questions, such as (1) the identity of stem cells and their input integration for initiating neurogenesis, (2) the nature of the neurogenic niche and neurogenesis without stem cell activity, (3) the complex functionality beyond the hippocampus, and (4) evolutionary and computational theory, including neurogenic neural networks for artificial intelligence.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"56 1","pages":"382-392"},"PeriodicalIF":23.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370993","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}
Cell stem cellPub Date : 2026-03-05DOI: 10.1016/j.stem.2026.02.004
Noor Radde,Max Jan
{"title":"Off-the-shelf CAR natural killer progenitor cell therapies are built to last.","authors":"Noor Radde,Max Jan","doi":"10.1016/j.stem.2026.02.004","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.004","url":null,"abstract":"Induced pluripotent stem cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cells are an emerging class of off-the-shelf cellular immunotherapy limited by short-term persistence. Wang et al.1 develop a platform for lineage-committed progenitor cell therapy to sustain in vivo CAR iNK cell lymphopoiesis and enhance tumor control.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"32 1","pages":"366-368"},"PeriodicalIF":23.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370999","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}
Cell stem cellPub Date : 2026-03-05DOI: 10.1016/j.stem.2026.02.001
Camilla Anastasio,Lucie Peduto
{"title":"Neuronal VIP shapes intestinal stem cell activity and mucosal immunity.","authors":"Camilla Anastasio,Lucie Peduto","doi":"10.1016/j.stem.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.001","url":null,"abstract":"Intestinal homeostasis and regeneration rely on intestinal stem cells (ISCs). Li et al.1 identified neuronal vasoactive intestinal peptide (VIP) as a brake on ISCs through VIPR1 to limit regeneration. In Nature Immunology, Jakob et al. and Pirzgalska et al. further showed that VIP-VIPR1 signaling restrains secretory lineage expansion and balances immune responses.2,3.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":"361-362"},"PeriodicalIF":23.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371003","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}
Cell stem cellPub Date : 2026-03-05DOI: 10.1016/j.stem.2026.02.005
Scott H Waddell,Luke Boulter
{"title":"Tissues assemble! Rebuilding the human periportal liver in a dish.","authors":"Scott H Waddell,Luke Boulter","doi":"10.1016/j.stem.2026.02.005","DOIUrl":"https://doi.org/10.1016/j.stem.2026.02.005","url":null,"abstract":"In their recent Nature paper, Yuan et al. reconstruct patient-specific periportal architecture by assembling hepatocyte organoids with cholangiocytes and portal mesenchyme. Unlike previous attempts, these multicellular units recapitulate much of the cell-cell interaction found in the adult human liver, providing a new sophisticated platform to understand liver biology.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"4 1","pages":"369-371"},"PeriodicalIF":23.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370995","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}