CellPub Date : 2026-10-01DOI: 10.1016/j.cell.2026.08.027
Minsoo Kim, Sarah E Calvo, Khanh Nguyen, Keith D Rivera, Namrata D Udeshi, Vamsi K Mootha
{"title":"A high-confidence plant mitochondrial proteome via protein correlation profiling.","authors":"Minsoo Kim, Sarah E Calvo, Khanh Nguyen, Keith D Rivera, Namrata D Udeshi, Vamsi K Mootha","doi":"10.1016/j.cell.2026.08.027","DOIUrl":"10.1016/j.cell.2026.08.027","url":null,"abstract":"<p><p>Plant mitochondria share many features with animal mitochondria but also possess unique traits, including presence of both circular and linear mitochondrial DNA, RNA editing, a branched electron transport chain, and metabolic pathways supporting photosynthesis. An accurate mitochondrial proteome is crucial for studying these conserved and lineage-specific functions. Here, we introduce a novel approach to defining plant mitoproteomes that combines serial mitochondrial enrichment, mass spectrometry, and protein correlation profiling. This approach allows us to experimentally define a mitochondrial protein inventory of 1,462 proteins with high sensitivity and specificity. Integration of our experimental inventory with literature and microscopy validation yields the Arabidopsisthaliana MitoCarta (AtMitoCarta) atlas of 1,609 mitochondrial proteins, including 236 newly defined proteins and 147 proteins of unknown functions. A comparative analysis across eukaryotic organisms reveals that 15% of mitochondrial protein families are plant specific, including expanded pentatricopeptide repeat proteins. The AtMitoCarta inventory and the experimental workflow applicable to wild-type plants will enable comparative studies of plant mitochondria.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"189 20","pages":"6267-6284.e9"},"PeriodicalIF":45.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104528","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}
CellPub Date : 2026-10-01Epub Date: 2026-09-01DOI: 10.1016/j.cell.2026.08.006
Raleigh M Linville, Benjamin T James, Kyriaki Galani, Li-Lun Ho, Jung Hoon Shin, Esaria Oliver, Stuart B Fass, James C Cameron, Brent E Fitzwalter, Roland Bock, Erin M Murray, Mathilde Louçã, Oluwamayowa Oke, Charlotte Wang, Erica Engelberg-Cook, Michael DeTure, Vanessa Farrell, Sergio Sebastian Pineda, Suphinya Sathitloetsakun, Xinyue Liang, Bertha Madras, Dennis W Dickson, Deborah C Mash, Gustavo Turecki, Vanessa C Wheeler, Veronica A Alvarez, Dana Gabuzda, Manolis Kellis, Myriam Heiman
{"title":"Cross-species single-cell atlas of the striatum defines cell-type and subregion disease vulnerabilities.","authors":"Raleigh M Linville, Benjamin T James, Kyriaki Galani, Li-Lun Ho, Jung Hoon Shin, Esaria Oliver, Stuart B Fass, James C Cameron, Brent E Fitzwalter, Roland Bock, Erin M Murray, Mathilde Louçã, Oluwamayowa Oke, Charlotte Wang, Erica Engelberg-Cook, Michael DeTure, Vanessa Farrell, Sergio Sebastian Pineda, Suphinya Sathitloetsakun, Xinyue Liang, Bertha Madras, Dennis W Dickson, Deborah C Mash, Gustavo Turecki, Vanessa C Wheeler, Veronica A Alvarez, Dana Gabuzda, Manolis Kellis, Myriam Heiman","doi":"10.1016/j.cell.2026.08.006","DOIUrl":"10.1016/j.cell.2026.08.006","url":null,"abstract":"<p><p>The striatum is critical for decision-making, movement, and reward processing, functions achieved through subregional cellular and molecular specialization. Striatal cell types and subregions are differentially implicated in neurodegenerative and neuropsychiatric disorders, but the mechanisms underlying these vulnerabilities are poorly understood. Using single-nucleus RNA sequencing across 109 human and 22 mouse samples spanning dorsal and ventral striatum, we provide a comprehensive atlas of subregional neuronal specialization. We define rare neuronal subpopulations and transcriptional gradients along the dorsolateral-ventromedial axis with notable differences between species, suggesting divergent pharmacological targets, connectivity, and disease mechanisms. Integration with genome-wide association and pharmacological studies identifies human-enriched sites of opioid receptor expression and ventral-biased chronic antipsychotic action. Lastly, paired single-cell transcriptomic and somatic trinucleotide repeat expansion measurements identify differences in subregion and neuronal subtype vulnerability in Huntington's disease. Our findings lay the foundation for understanding how striatal cell types and subregions contribute to brain function and neurological disorders.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"6490-6521.e19"},"PeriodicalIF":45.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872808","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}
CellPub Date : 2026-09-30DOI: 10.1016/j.cell.2026.09.047
Gabriela Prus, Shankha Satpathy, Brian T Weinert, Takeo Narita, Chunaram Choudhary
{"title":"Global, site-resolved analysis of ubiquitylation occupancy and turnover rate reveals systems properties.","authors":"Gabriela Prus, Shankha Satpathy, Brian T Weinert, Takeo Narita, Chunaram Choudhary","doi":"10.1016/j.cell.2026.09.047","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.047","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":45.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104578","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}
CellPub Date : 2026-09-30DOI: 10.1016/j.cell.2026.09.011
Yixuan Chen, John Withers, Yulin Sun, Tianyuan Chen, Sargis Karapetyan, Jan Draken, Yezi Xiang, Yuzhe Yuan, Yang He, Wolfgang Dröge-Laser, Jing-Ke Weng, Xinnian Dong
{"title":"Salicylic acid engages central metabolic regulators SnRK1 and TOR to govern immunity by differential phosphorylation of NPR1.","authors":"Yixuan Chen, John Withers, Yulin Sun, Tianyuan Chen, Sargis Karapetyan, Jan Draken, Yezi Xiang, Yuzhe Yuan, Yang He, Wolfgang Dröge-Laser, Jing-Ke Weng, Xinnian Dong","doi":"10.1016/j.cell.2026.09.011","DOIUrl":"10.1016/j.cell.2026.09.011","url":null,"abstract":"<p><p>Immunity requires a delicate balance between combating infection and preserving metabolic functions. However, the mechanisms by which immune responses are coordinated with cellular metabolism remain largely unknown. Here, we show that NONEXPRESSER OF PR GENES 1 (NPR1), the central plant immune regulator of salicylic acid (SA)-mediated defense responses, is controlled by a cascade of post-translational modifications (PTMs) involving two master nutrient-sensing kinases. In the absence of pathogen challenge, TARGET OF RAPAMYCIN (TOR) inhibits NPR1 through phosphorylation at Ser-55/59. During defense responses, elevated SA reduces sugar phosphate levels and enhances SNF1-RELATED PROTEIN KINASE 1 (SnRK1) activity, which in turn inhibits TOR signaling and phosphorylates NPR1 at Ser-557, a modification required for subsequent PTMs and NPR1 activation. Together, our findings identify SA as a coordinator of growth and immunity in response to pathogen challenge by modulating the central metabolic regulators SnRK1 and TOR, which antagonistically control NPR1 immune activity through differential phosphorylation.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":45.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104549","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}
CellPub Date : 2026-09-29DOI: 10.1016/j.cell.2026.09.009
Lu Yang,Vaidhvi Singh,Brent J. Gawey,Jason P. Sinnwell,Stephen Johnson,Elle C. Billings,Trena M. Van Gorp,Jonathan J. Harrington,Michael Q. Slama,Lisa M. Till,Manavjot Singh,Thoshik R. Samineni,Mojun Zhu,Krishna R. Kalari,Gianrico Farrugia,Jun Chen,Ruben A.T. Mars,Purna C. Kashyap
{"title":"Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort","authors":"Lu Yang,Vaidhvi Singh,Brent J. Gawey,Jason P. Sinnwell,Stephen Johnson,Elle C. Billings,Trena M. Van Gorp,Jonathan J. Harrington,Michael Q. Slama,Lisa M. Till,Manavjot Singh,Thoshik R. Samineni,Mojun Zhu,Krishna R. Kalari,Gianrico Farrugia,Jun Chen,Ruben A.T. Mars,Purna C. Kashyap","doi":"10.1016/j.cell.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.009","url":null,"abstract":"The gut microbiome has emerged as a key contributor to cancer biology. Prior studies have focused on individual cancers and often overlook comorbidities, obscuring whether reported associations are specific to a cancer type. Here, we present findings from a real-world mixed-cancer cohort (Mayo Clinic Cancer Microbiome), comprising 1,364 cancer patients and 287 healthy controls. By applying a framework to account for non-specific microbiome associations with cancer, comorbidities, and demographic and clinical variables, we identified 341 cancer-associated species across five cancer classes that represent the most plausible contributors to cancer pathogenesis. Within cancer classes, we found lower levels of fecal bile acids and C. scindens in early-onset breast cancer and elevated lactate and Veillonella parvula in early-onset colorectal cancer. Additionally, Anaerostipes hadrus encoding dihydropyrimidine dehydrogenase was protective against 5-fluorouracil-induced diarrhea. These findings demonstrate the strength of our cohort and provide a foundational resource for the discovery of cancer-specific microbiome signatures and predictive biomarkers.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"23 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070987","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}
CellPub Date : 2026-09-29DOI: 10.1016/j.cell.2026.09.012
Yumeng Hu,Gaoyuan Lv,Hao Yuan,Zhijun Zhou,Shaobo Zhang,Yuxin Ye,Qun Chen,Yang Cai,Jingxuan Yang,Yuqing Zhang,Chao Xu,Wenyi Luo,Michael S. Bronze,Courtney W. Houchen,Yi-Ping Li,Jingyong Xu,Yuanyuan Zhang,Mingyang Liu,Min Li
{"title":"Spatial evolution of a cachexia-promoting microenvironment in pancreatic cancer","authors":"Yumeng Hu,Gaoyuan Lv,Hao Yuan,Zhijun Zhou,Shaobo Zhang,Yuxin Ye,Qun Chen,Yang Cai,Jingxuan Yang,Yuqing Zhang,Chao Xu,Wenyi Luo,Michael S. Bronze,Courtney W. Houchen,Yi-Ping Li,Jingyong Xu,Yuanyuan Zhang,Mingyang Liu,Min Li","doi":"10.1016/j.cell.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.012","url":null,"abstract":"Cachexia is a major cause of morbidity in pancreatic cancer, but the cellular circuitry linking tumor progression to systemic wasting remains incompletely understood. Integrating single-cell RNA sequencing, Xenium spatial transcriptomics, multiplex immunohistochemistry, bulk transcriptomics, and functional studies across human non-cachexia, pre-cachexia, and cachexia samples, together with mouse models, we define a cachexia-associated microenvironmental niche composed of SEMA4A+ tumor cells, AQP9+ macrophages, and LOXL2+ cancer-associated fibroblasts. Mechanistically, SEMA4A-associated signaling promotes bone morphogenetic protein-2 (BMP2)-dependent acquisition of an AQP9-associated macrophage phenotype, and macrophage-derived CXCL8 activates LOXL2+ fibroblasts. LOXL2+ fibroblasts reciprocally enhance tumor cell FOSL1/SEMA4A signaling through exosomal N-glycosylated LOXL2. Spatial analyses demonstrate progressive enrichment of this niche with cachexia severity and association with postoperative development of cachexia in previously non-cachectic patients. These findings provide a framework linking local tumor ecosystem dynamics to cachexia progression.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"12 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070986","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":"Gut microbiota primes stroke severity via the AHR in intestinal dendritic cells","authors":"Rosa Delgado Jiménez,Alexandria Ruggles,Mujeeb Adekunle Adedokun,Adam Sorbie,Diana Fink,Samuele Laudani,Alba Simats,Yufei He,Vanessa Pahl,Laura Díaz-Marugán,Morten Voss,Kartikeya Singh,Miquel Lledós,Olga Carofiglio,Philip Melton,Kelsey Pinkham,Alessio Ricci,Stefan Roth,Rebecca Sadler,Svetlina Khayat,Seyedeh Maryam Mousavi,Thanos Tsaktanis,Ann-Marie Tobinski,Carolin Walter,Caspar Ohnmacht,Jochen Huehn,Johannes Herkel,Antonella Carambia,Luisa Klotz,Mathias Gelderblom,Veit Rothhammer,Tommy Regen,Jürgen Bernhagen,Michael Gigl,Michael Zimmermann,Israel Fernandez-Cadenas,Lorenz Hirt,Michael Delacher,Arthur Liesz,Corinne Benakis","doi":"10.1016/j.cell.2026.09.013","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.013","url":null,"abstract":"The gut microbiota modulates systemic immunity and neurological diseases, yet the underlying mechanisms remain unclear. Here, we identify the enrichment of indole-producing Escherichia coli being associated with worse outcomes in mice and patients with ischemic stroke. Microbial indole triggers an aryl hydrocarbon receptor (AHR)-dependent response in dendritic cells (DCs). DC-specific AHR deletion improves stroke outcomes and preserves intestinal conventional type 1 DCs. AHR deletion also promotes immunoregulatory and migratory transcriptional signatures and enhances CCR7-dependent migration in vitro. Pharmacological AHR inhibition favors gut-derived DC accumulation in the meninges, accompanied by increased regulatory T cells (Tregs) and reduced neuroinflammation, while Treg depletion abolishes the neuroprotection conferred by AHR inhibition. Detrimental effects of indole-producing Escherichia coli, indole administration, and microbiota transplantation from patients with stroke are attenuated in DC-specific AHR-deficient mice. These findings define a microbiota-AHR axis that programs intestinal immune responses before brain injury and highlight microbial tryptophan metabolism as a tractable therapeutic target.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"35 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070993","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":"Cargo crosslinking nucleates AP-1 lattice formation","authors":"Huaqing Deng,Guowen Jia,Qin Yang,Lin Zhao,Ping Li,Min Ling,Jiaqi Fan,Yingfeng Tu,Xin Yong,Ying Lai,Zhaoming Su,Da Jia","doi":"10.1016/j.cell.2026.09.022","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.022","url":null,"abstract":"Vesicle trafficking is critical for proper distribution of proteins and lipids within eukaryotic cells. This process relies on the selective incorporation of cargo into transport carriers by coat systems, including adaptor-clathrin complexes. While the molecular basis of cargo recognition is well established, the extent to which cargo contributes directly to coat assembly remains incompletely understood. Here, we present cryo-electron microscopy (cryo-EM) structures of the human AP-1 complex bound to a cargo containing tandem sorting motifs at resolutions of 3.5 and 4.0 Å. The structures reveal that a single cargo molecule bearing tandem motifs can bridge two neighboring AP-1 complexes through a previously unrecognized μ1-σ1 inter-complex interface, thereby promoting adaptor oligomerization. Critically, this interface contributes to efficient AP-1-clathrin cage assembly, cargo trafficking, and neuronal development in zebrafish. Together, these findings support a model in which cargo engagement can facilitate higher-order adaptor assembly under physiological conditions, complementing established coat-driven mechanisms.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"40 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067357","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}
CellPub Date : 2026-09-28DOI: 10.1016/j.cell.2026.09.004
Markus Perl,Severin Guetter,Dhyani Shah,Simon Holzinger,Luisa Becker,Misbah Tariq,Phillipp Menauer,Simon Delahais,Gloria Lutzny-Geier,Julian N. Scherer,Sascha Göttert,Konstantin Herfeld,Paul Heinrich,Klaus Georg Kreitmeier,Claudia Gebhard,Wolfgang Herr,Marcel P. Trefny,Janina Doerr,Saba Sameri,Dennis C. Harrer,Kai Ziegler-Martin,Sarah Staudt,Leo Hansmann,Matthias Edinger,Daniel Wolff,Daniela Weber,Elisabeth Meedt,Alexander Denk,Andre Gessner,Ernst Holler,Tobias Wertheimer,Klaus Neuhaus,Tingting Zheng,David M. Cordas Dos Santos,Sebastian Theurich,Melanie Schirmer,Karin Kleigrewe,Jonas Schluter,Marcel van den Brink,Michael Schmitt,Markus Feuerer,Christoph Heuser-Loy,Jeremy Baldwin,Luca Gattinoni,Michael Rehli,Michael Hudecek,Camille Bigenwald,Laurence Zitvogel,Marion Subklewe,Viktoria Blumenberg,Maria-Luisa Schubert,Christoph Stein-Thoeringer,Maik Luu,Sebastian Kobold,Matthias A. Fante,Erik Thiele Orberg,Hendrik Poeck
{"title":"Opposing functions of gut immunomodulatory metabolites on CAR-T therapy","authors":"Markus Perl,Severin Guetter,Dhyani Shah,Simon Holzinger,Luisa Becker,Misbah Tariq,Phillipp Menauer,Simon Delahais,Gloria Lutzny-Geier,Julian N. Scherer,Sascha Göttert,Konstantin Herfeld,Paul Heinrich,Klaus Georg Kreitmeier,Claudia Gebhard,Wolfgang Herr,Marcel P. Trefny,Janina Doerr,Saba Sameri,Dennis C. Harrer,Kai Ziegler-Martin,Sarah Staudt,Leo Hansmann,Matthias Edinger,Daniel Wolff,Daniela Weber,Elisabeth Meedt,Alexander Denk,Andre Gessner,Ernst Holler,Tobias Wertheimer,Klaus Neuhaus,Tingting Zheng,David M. Cordas Dos Santos,Sebastian Theurich,Melanie Schirmer,Karin Kleigrewe,Jonas Schluter,Marcel van den Brink,Michael Schmitt,Markus Feuerer,Christoph Heuser-Loy,Jeremy Baldwin,Luca Gattinoni,Michael Rehli,Michael Hudecek,Camille Bigenwald,Laurence Zitvogel,Marion Subklewe,Viktoria Blumenberg,Maria-Luisa Schubert,Christoph Stein-Thoeringer,Maik Luu,Sebastian Kobold,Matthias A. Fante,Erik Thiele Orberg,Hendrik Poeck","doi":"10.1016/j.cell.2026.09.004","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.004","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell therapy has transformed hematological cancer treatment, yet nearly half of patients still relapse or progress. Increasing evidence implicates the gut microbiome and antibiotic exposure as key modulators of clinical outcomes. In a cohort of 129 patients across three German centers, shotgun metagenomics and targeted mass spectrometry revealed that reduced short-chain fatty acids, particularly valeric acid, prior to CAR-T cell therapy correlated with increased risk of disease progression. Conversely, high levels of indole metabolites, including indole-3-carboxaldehyde and indole-3-acetic acid as well as the branched-chain fatty acid isovaleric acid, were linked to adverse outcomes. Functional validation in human and murine CAR-T cell models demonstrated that valeric acid supplementation enhanced, while indole-3-carboxaldehyde and isovaleric acid impaired, CAR-T cell efficacy. These findings reveal the opposing roles of immunomodulatory metabolites on CAR-T cell therapy, carrying significant implications for the design of metabolite-guided, microbiome-based therapeutics.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"15 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067356","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}
CellPub Date : 2026-09-28DOI: 10.1016/j.cell.2026.09.005
Daesun Song,Marigold Gil Malinao,Xiang Wu,Shan Jiang,Dongyun Jiang,Michael Westberg,Yichi Su,Sa Cai,Dongin Lee,Nicole A. Repina,David V. Schaffer,Hanlee P. Ji,Guosong Hong,Michael Z. Lin
{"title":"Non-invasive control of gene editing in vivo by photoswitchable Cas12f and focused ultrasound","authors":"Daesun Song,Marigold Gil Malinao,Xiang Wu,Shan Jiang,Dongyun Jiang,Michael Westberg,Yichi Su,Sa Cai,Dongin Lee,Nicole A. Repina,David V. Schaffer,Hanlee P. Ji,Guosong Hong,Michael Z. Lin","doi":"10.1016/j.cell.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.005","url":null,"abstract":"A spatiotemporally controllable CRISPR-Cas system would be highly desirable for restricting gene editing to specific times and locations in vivo. Ideally, such a system would be compatible with tissue- or cell-type-specific delivery by adeno-associated virus (AAV) and could be controlled from outside the body. However, neither the delivery of controllable CRISPR-Cas systems by single AAV particles nor their noninvasive activation deep within tissue has yet been achieved. In this study, we address both of these limitations. We engineer compact photoswitchable Cas12f (psCas12f) proteins that are co-deliverable with their single guide RNA (sgRNA) in a single AAV particle. We then activate psCas12f in vivo using focused ultrasound (FUS) and mechanoluminescent particles, enabling precise spatiotemporal control. We demonstrate successful gene editing in the targeted skeletal muscle and brain regions of mice using AAV-transduced psCas12f and FUS. In summary, we describe a completely noninvasive method for localized gene editing in vivo.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"219 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067358","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}
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