Cell最新文献

{"title":"Sulfur partitioning from cysteine controls T cell proliferation and effector function.","authors":"Beth Kelly, Minsun Cha, Tatjana Gremelspacher, Jacob L Martin, Massimo Andreis, Isha Maloo, Gustavo E Carrizo, Mia Gidley, Michal A Stanczak, Petya Apostolova, Joseph Longo, Lisa M DeCamp, Eric H Ma, Ryan D Sheldon, Russell G Jones, David E Sanin, Ananya Majumdar, Erika L Pearce","doi":"10.1016/j.cell.2026.03.012","DOIUrl":"10.1016/j.cell.2026.03.012","url":null,"abstract":"<p><p>Delineating how acquired nutrients are partitioned into different intracellular pathways and how these various fates support distinct functions in T cells is limited. We show that CD8⁺ T cells acquire cysteine to serve both as a substrate for glutathione (GSH) production, which modulates effector functions, and to cede its sulfur for NFS1-dependent FeS cluster synthesis, which supports proliferation. NFS1 deletion in activated CD8⁺ T cells promotes exhaustion and dampens anti-cancer immunity, whereas blocking cysteine flux into GSH or enforcing FeS metabolism enhances tumor control. This role for disrupted FeS metabolism in T cell exhaustion is echoed in data from human hepatocellular carcinoma. Elucidating how different intracellular pathways use cysteine enables targeted control of cysteine flux to retain the beneficial effects of cysteine while abolishing those that restrain function. We illustrate this concept for one metabolite, cysteine, but it is likely to apply to other metabolites relevant for immune cell function.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phages communicate across species to shape microbial ecosystems","authors":"Francisca Gallego-del-Sol, Daniel Sin, Cora Chmielowska, Javier Mancheño-Bonillo, Yuyi Li, Sara Zamora-Caballero, Nuria Quiles-Puchalt, José R. Penadés, Alberto Marina","doi":"10.1016/j.cell.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.004","url":null,"abstract":"Arbitrium is a communication system that helps bacteriophages to decide between lysis and lysogeny through secreted peptides. In this system, the arbitrium communication peptide (AimP) binds its cognate arbitrium receptor (AimR) to repress <em>aimX</em> (a negative regulator of lysogeny) expression, promoting lysogeny. It has been assumed that each AimR responds exclusively to its own AimP. Here, we challenge this view by demonstrating cross-communication between arbitrium systems. Using prototypical arbitrium phages, we show that AimP peptides can bind and repress non-cognate AimR receptors, promoting lysogeny and reducing prophage induction. Structural and biochemical analyses reveal conserved receptor features that permit cross-recognition of non-cognate peptides while preserving recognition of cognate partners. In mixed lysogenic cultures, these interactions alter induction outcomes, underscoring their ecological significance. Extending to infection contexts, we demonstrate that crosstalk favors lysogeny of incoming phages in cells harboring compatible systems. These findings establish that phages engage in cross-species communication via peptide signaling, reshaping microbial communities in unexpected ways.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"58 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy.","authors":"Zeda Zhang, Yu-Jui Ho, Xin Fang, Minseo Kim, Marguerite Li, Wei Luan, Clemens Hinterleitner, Sascha Haubner, Friederike Kogel, Edwin C Pratt, Elif Ozcelik, José Reyes, Qingwen Jiang, Vincent W Yang, Yu-Jung Chen, Tao Wang, Haijiao Liu, Haonan Hu, Xueqian Zhuang, Jin Park, Stella V Paffenholz, Kevin Chen, Qing Chang, Amanda Kulick, Jing Zhang, Eric Chan, Eric Rosiek, Ning Fan, Riley A Williams, Adam C Wang, Samuel Freeman, Sha Tian, Gertrude Gunset, Andreina Garcia Angus, Nicolas Lecomte, Selma Yeni Yildirim, Emily Ali, Michelle Wu, Ileana C Miranda, Cristina R Antonescu, Olca Basturk, Zeynep Tarcan, Natasha Rekhtman, Christina Wilson, Merve Basar, Jennifer L Sauter, Hikmat A Al-Ahmadie, Samuel Singer, Christine Iacobuzio-Donahue, Charles Rudin, Elisa de Stanchina, Karuna Ganesh, Paul B Romesser, Britta Weigelt, Dan Dongeun Huh, Josef Leibold, Judith Feucht, Ignacio Vázquez-García, Matthew J Bott, Dmitriy Zamarin, Sohrab P Shah, Jason S Lewis, Corina Amor, Dana Pe'er, Jorge Mansilla-Soto, Aveline Filliol, Michel Sadelain, Scott W Lowe","doi":"10.1016/j.cell.2026.03.002","DOIUrl":"10.1016/j.cell.2026.03.002","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells have transformed hematologic cancer therapy but remain limited in solid tumors by antigen heterogeneity and a suppressive, pro-fibrotic microenvironment. We previously identified the urokinase plasminogen activator receptor (uPAR) as upregulated in senescent, pro-fibrotic cells and showed that uPAR-directed CAR T cells could safely reverse fibrosis in mice. Integrative analyses now reveal that uPAR is broadly expressed in solid tumors enriched for TP53 and RAS pathway mutations. These tumors adopt a progenitor-like state supported by a niche of uPAR-positive stromal cells with senescence features. Human uPAR CAR T cells eliminate tumor cells and their stromal support, induce durable regressions across diverse models, eradicate systemic metastases, and are potentiated by senescence-inducing therapies. Importantly, these cells achieve robust antitumor activity without sustained myelosuppression in mice reconstituted with human immune systems. Together, these findings establish uPAR as a broadly applicable CAR T target capable of overcoming major barriers in solid tumor therapy.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-body molecular and cellular mapping of the laboratory mouse","authors":"Margarette H. Clevenger, Denis Cipurko, Ashwini Patil, Bohan Li, Michihiro Takahama, Linghan Mei, Madison Plaster, Gabriella Richey, Tadafumi Kawamoto, Feng Bao, Nicolas Chevrier","doi":"10.1016/j.cell.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.006","url":null,"abstract":"The laboratory mouse is a key model system for biomedical research, yet body-wide measurement tools are lacking. Here, we generate spatiotranscriptomics profiles of whole-mouse sections that accurately capture histological regions. We spatially assign 379 cell types across whole-mouse section profiles by building a reference dataset of 59M single cells coupled with a scalable computational method for cell-type assignment. Moreover, we exploit these whole-mouse profiles to create a machine learning pipeline, LABEL, which enables pan-body annotation of tissues and cell types on histology images from H&amp;E-stained sections. Lastly, we apply whole-mouse spatial profiling to map systemic inflammation in endotoxemia, which delineates organism-wide changes in gene expression programs across tissues and cell types. Together, our work paves the way for body-wide studies of the molecular and cellular processes that govern the organismal biology of the laboratory mouse across space, time, and conditions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"11 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing precision health discovery in a genetically diverse health system","authors":"Roni Haas, Michael P. Margolis, Angela Wei, Takafumi N. Yamaguchi, Jeffrey Feng, Thai Tran, Veronica Tozzo, Katelyn J. Queen, Mohammed Faizal Eeman Mootor, Vishakha Patil, Michael E. Broudy, Paul Tung, Shafiul Alam, Danielle B. Martinez, Yash Patel, Christa Caggiano, Nicole Zeltser, Rupert Hugh-White, Jaron Arbet, Ruhollah Shemirani, Daniel H. Geschwind","doi":"10.1016/j.cell.2026.03.007","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.007","url":null,"abstract":"Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. We analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. We discovered numerous unreported gene-phenotype associations, including <em>FN3K</em> with intestinal disaccharidase deficiency in Europeans and admixed Americans. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, we reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations, including <em>ANKZF1</em> and peripheral vascular disease in African Americans. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes, and is modulated by genetic variation in <em>PTPRU</em>. These findings illustrate how ancestrally diverse biobanks from a single health system yield robust disease associations and pharmacogenomic insights.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"318 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STING signaling modulation by COPII cargo recognition","authors":"Heng Lyu, Cong Xing, Wanwan Huai, Kun Song, Devon Jeltema, Hui Zhang, Xuewu Zhang, Nan Yan","doi":"10.1016/j.cell.2026.02.029","DOIUrl":"https://doi.org/10.1016/j.cell.2026.02.029","url":null,"abstract":"Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive. Here, we identify EEΦxΦ (³³⁹EEVTV³⁴³ in human STING) as the ER-exit motif recognized by SEC24 homolog C (SEC24C). Using AlphaFold3, we present a predicted structure of SEC24C binding to a STING dimer, revealing the EEΦxΦ motif in a previously structurally unresolved region. Mutations in this motif or the SEC24C cargo-binding site disrupt STING trafficking and signaling. Our findings support a STING oligomerization and avidity threshold model that explains regulated ER exit. The EEΦxΦ motif is conserved in vertebrate STING homologs and is sufficient to mediate ER exit of unrelated proteins. Interestingly, the STING ER-exit motif is suboptimal compared with known SEC24C cargos, which is crucial for preventing immune overactivation. An engineered “super-ER-exit” STING is constitutively active and induces potent antitumor immunity. Tandem repeats of this motif competitively inhibit endogenous STING signaling. Collectively, this study elucidates the STING-ER-exit mechanism and presents strategies for modulating STING signaling.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of non-spatial grid-like neural codes tracks inference and intelligence","authors":"Yukun Qu, Jianxin Ou, Luoyao Pang, Shuqi Wu, Yuejia Luo, Tim Behrens, Yunzhe Liu","doi":"10.1016/j.cell.2026.02.028","DOIUrl":"https://doi.org/10.1016/j.cell.2026.02.028","url":null,"abstract":"Piaget’s theory posits that children develop structured knowledge schemas for inferring and assimilating new information, yet the underlying neural mechanisms remain unclear. In 203 participants aged 8–25 years, we investigated how maturation of a two-dimensional (2D) knowledge map underpins inferential reasoning and knowledge assimilation. Grid-cell-like codes in the entorhinal cortex (EC) strengthened with age, reflecting schema representations in non-spatial conceptual spaces, and predicted improved inferential reasoning. These grid-like codes also supported the medial prefrontal cortex (mPFC) in encoding distance relationships between objects on the 2D map. As participants assimilated new information, they integrated it into existing grid patterns in the EC. Moreover, the maturation of these neural codes tracked real-world intelligence measures, particularly reasoning abilities. Our findings demonstrate that the development of non-spatial grid-like neural codes offers a mechanistic account of cognitive development, bridging psychological theory with a fundamental cellular representation of the cognitive map.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"219 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures","authors":"Him K. Shrestha, Huan Sun, Jay M. Yarbro, DongGeun Lee, Danting Liu, Erming Wang, Meghan McReynolds, Nan Zhang, Boer Xie, Shu Yang, Kaiwen Yu, Suresh Poudel, Yuxin Li, Zuo-Fei Yuan, Dehui Kong, Minghui Wang, Zhen Wang, Mingming Niu, Hong Wang, Masihuz Zaman, Ju Wang, David R. Vanderwall, Yu Sun, Zhiping Wu, Ping-Chung Chen, Bing Bai, Anthony A. High, Júlia Faura, Chunyu Liu, David A. Bennett, Erik C.B. Johnson, Nicholas T. Seyfried, Allan I. Levey, Vahram Haroutunian, Geidy E. Serrano, Thomas G. Beach, Michael DeTure, Takahisa Kanekiyo, Ronald C. Petersen, Guojun Bu, Pamela J. McLean, Dennis W. Dickson, Rosa Rademakers, Gang Yu, Xusheng Wang, Bin Zhang, Junmin Peng","doi":"10.1016/j.cell.2026.02.026","DOIUrl":"https://doi.org/10.1016/j.cell.2026.02.026","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"3 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BMP Inhibitor Coco Reactivates Breast Cancer Cells at Lung Metastatic Sites","authors":"Hua Gao, Goutam Chakraborty, Ai Ping Lee-Lim, Qianxing Mo, Markus Decker, Alin Vonica, Ronglai Shen, Edi Brogi, Ali H. Brivanlou, Filippo G. Giancotti","doi":"10.1016/j.cell.2026.03.026","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.026","url":null,"abstract":"(Cell <em>150</em>, 764–779; August 17, 2012)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"50 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An activated wheat CC_G10-NLR immune receptor forms an octameric resistosome.","authors":"Guanghao Guo, He Zhao, Kaihong Bai, Jian Lu, Qiuhong Wu, Lei Lu, Yue Zhang, Lingli Dong, Guangwei Li, Yongxing Chen, Yikun Hou, Ping Lu, Miaomiao Li, Huaizhi Zhang, Gaojie Wang, Keyu Zhu, Baoge Huang, Xuejia Cui, Hongkui Fu, Chenchen Hu, Zhiying Chu, Xue Lyu, Sophien Kamoun, Chao Wang, Zhiyong Liu, Muniyandi Selvaraj, Jonathan D G Jones","doi":"10.1016/j.cell.2026.02.024","DOIUrl":"https://doi.org/10.1016/j.cell.2026.02.024","url":null,"abstract":"<p><p>Nucleotide-binding, leucine-rich repeat (NLR) receptors are widespread intracellular immune sensors across kingdoms. Plant G10-type coiled-coil (CC_G10)-NLRs constitute a distinct phylogenetic clade that remains poorly characterized. Here, we identified a gain-of-function mutant of wheat autoimmunity 3 (WAI3^GOF), which encodes a constitutively active CC_G10-NLR resulting from a residue substitution in the leucine-rich repeat (LRR) domain. Cryo-electron microscopy (cryo-EM) analysis reveals that activated WAI3 assembles into a distinctive octameric resistosome. Arabidopsis RPS2, another CC_G10-NLR, also forms an octamer, indicating a conserved structural property across monocot and dicot plants. The WAI3 resistosome induces a prolonged and sustained increase in cytosolic calcium, likely facilitated by a unique channel architecture arising from its divergent coiled-coil (CC) domain configuration. Notably, this domain arrangement may be shared by plant NLRs that lack the conserved EDVID (Glu-Asp-Val-Ile-Asp) motif in their CC domains. Together, our findings uncover a conserved yet previously uncharacterized NLR resistosome structure and provide insights into the plant immune receptor plasticity.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}