CellPub Date : 2026-10-29DOI: 10.1016/j.cell.2026.09.056
Lena Alexopoulou,Rejane Rua
{"title":"Guardians at the gate: cMAF keeps the brain’s vasculature in check","authors":"Lena Alexopoulou,Rejane Rua","doi":"10.1016/j.cell.2026.09.056","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.056","url":null,"abstract":"In this issue of Cell, Brioschi et al. identify cellular musculoaponeurotic fibrosarcoma (cMAF) as a key regulator of brain perivascular macrophages that supports cerebrovascular function through insulin-like growth factor 1 (IGF1) production. This cMAF-IGF1 program is enhanced in Alzheimer’s disease (AD), potentially reflecting a protective response that is lost in APOE4 carriers.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"64 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281658","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 : 2026-10-29Epub 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":"10.1016/j.cell.2026.09.047","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"7253-7254"},"PeriodicalIF":45.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730015/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellPub Date : 2026-10-29Epub Date: 2026-09-11DOI: 10.1016/j.cell.2026.08.024
Zhi-Luo Deng, Nasim Safaei, Alice Carolyn McHardy
{"title":"Metax enables accurate cross-domain taxonomic profiling of metagenomes.","authors":"Zhi-Luo Deng, Nasim Safaei, Alice Carolyn McHardy","doi":"10.1016/j.cell.2026.08.024","DOIUrl":"10.1016/j.cell.2026.08.024","url":null,"abstract":"<p><p>Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"7196-7211.e7"},"PeriodicalIF":45.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944171","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 : 2026-10-29Epub Date: 2026-08-28DOI: 10.1016/j.cell.2026.08.002
Ronghui Zhu, Emma Dann, Jun Yan, Justine Reyes Retana, Ryunosuke Goto, Reese C Guitche, Lillian Brixi, Mineto Ota, Austin Hartman, Theodore L Roth, Ansuman T Satpathy, Jonathan K Pritchard, Alexander Marson
{"title":"Genome-scale perturb-seq in primary human CD4<sup>+</sup> T cells maps context-specific regulators of T cell programs and human immune traits.","authors":"Ronghui Zhu, Emma Dann, Jun Yan, Justine Reyes Retana, Ryunosuke Goto, Reese C Guitche, Lillian Brixi, Mineto Ota, Austin Hartman, Theodore L Roth, Ansuman T Satpathy, Jonathan K Pritchard, Alexander Marson","doi":"10.1016/j.cell.2026.08.002","DOIUrl":"10.1016/j.cell.2026.08.002","url":null,"abstract":"<p><p>Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, we perturbed all expressed genes across 22 million primary human CD4<sup>+</sup> T cells from four donors and developed a probe-based perturb-seq platform to measure the transcriptome effects in cells at rest and after stimulation. These data allowed us to map genes regulating immune pathways, including previously uncharacterized regulators of cytokine production. Importantly, active regulators and the gene programs they control changed dramatically across stimulation conditions. Perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of T cell polarization and of age-related phenotypes. Finally, we leveraged perturb-seq to implicate context-specific gene regulatory pathways in autoimmune disease risk. Our study provides a foundational resource and new approaches to decode T cell function and human immune traits.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"6988-7012.e17"},"PeriodicalIF":45.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849983","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 : 2026-10-29DOI: 10.1016/j.cell.2026.09.018
Jonathan D.G. Jones,Caixia Gao
{"title":"Roads not taken: The mismatch between safety and regulation of plant breeding innovation","authors":"Jonathan D.G. Jones,Caixia Gao","doi":"10.1016/j.cell.2026.09.018","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.018","url":null,"abstract":"Meeting global food security goals while reducing agriculture’s environmental impact requires continued crop improvement and innovation. Advances in transgenesis, cisgenesis, and genome editing now enable increasingly precise genetic modification with risks comparable to those of conventional breeding, yet regulatory frameworks remain focused on the method used rather than the product. We highlight recent examples, including immune receptor transfer, cisgenesis-based disease resistance stacking, photosynthesis engineering, and AI-guided protein design, that illustrate innovations constrained by current regulatory approaches. A decisive shift toward science-based, proportionate, and product-focused regulation is needed so that improved crops are evaluated on the basis of their properties, not how they were made.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281655","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 : 2026-10-29Epub Date: 2026-08-25DOI: 10.1016/j.cell.2026.07.039
Pengfei Guo, Yan Cui, Jincan He, Abraham J Waldman, Jiaxin Zhu, Yufan Chen, Zhi Huang, Jingtian Zhou, Jennifer E Phillips-Cremins, Yanxiang Deng
{"title":"Integrative spatial profiling of 3D genome organization and gene expression in tissue.","authors":"Pengfei Guo, Yan Cui, Jincan He, Abraham J Waldman, Jiaxin Zhu, Yufan Chen, Zhi Huang, Jingtian Zhou, Jennifer E Phillips-Cremins, Yanxiang Deng","doi":"10.1016/j.cell.2026.07.039","DOIUrl":"10.1016/j.cell.2026.07.039","url":null,"abstract":"<p><p>Three-dimensional genome organization shapes transcriptional regulation, yet measuring its spatial coordination in situ within intact tissues remains challenging. We present Spatial Hi-C-RNA, a multimodal platform that simultaneously maps genome-wide chromatin contacts and transcriptomes from the same tissue section at near-single-cell resolution. Across the mouse brain, developing embryos, and human melanoma, Spatial Hi-C-RNA generated multimodal maps that aligned with tissue anatomy while revealing complementary chromatin- and RNA-defined spatial patterns. Multiscale features, including A/B compartments, topologically associating domains, and chromatin loops, were associated with region- and cell-type-specific transcriptional programs. In mouse embryos, Spatial Hi-C-RNA resolved coordinated chromatin and transcriptional remodeling during neuronal maturation across developmental stages. In human melanoma, chromatin architecture delineated intratumoral subregions not detected by RNA alone and linked tumor-state transitions to changes in compartments, domain boundaries, and regulatory programs. Spatial Hi-C-RNA thus provides a broadly applicable framework for investigating genome structure-function relationships in development and disease within native tissue environments.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"7177-7195.e11"},"PeriodicalIF":45.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817528","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 : 2026-10-29DOI: 10.1016/j.cell.2026.10.004
Kojiro Mukai,Dongya Jia,Mamata Panigrahi,Thomas Tayman,Graham Brogden,Ying-Han Chen,Nazmul Haque,Gunjan Arora,Joshua E. Mutterperl,Ian Poe,Chenyu Zhang,Zahin Islam,Ronald Holewinski,Thorkel Andresson,Di Wu,Grzegorz Piszczek,Joseph Marcotrigiano,J. Robert Hogg,Suk See De Ravin,Nasir S. Malik,Avindra Nath,Ekaterina Viktorova,Anna Zimina,George A. Belov,Banu Bayyurt-Kocabaş,Grégoire Altan-Bonnet,Nihal Altan-Bonnet
{"title":"Innate sensor responses set a supra-unitary threshold for viral replication","authors":"Kojiro Mukai,Dongya Jia,Mamata Panigrahi,Thomas Tayman,Graham Brogden,Ying-Han Chen,Nazmul Haque,Gunjan Arora,Joshua E. Mutterperl,Ian Poe,Chenyu Zhang,Zahin Islam,Ronald Holewinski,Thorkel Andresson,Di Wu,Grzegorz Piszczek,Joseph Marcotrigiano,J. Robert Hogg,Suk See De Ravin,Nasir S. Malik,Avindra Nath,Ekaterina Viktorova,Anna Zimina,George A. Belov,Banu Bayyurt-Kocabaş,Grégoire Altan-Bonnet,Nihal Altan-Bonnet","doi":"10.1016/j.cell.2026.10.004","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.004","url":null,"abstract":"Cells resist viral infection by triggering rapid and sensitive innate immune responses, initiated by cytoplasmic viral sensor proteins (CyVSP), retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated protein 5 (MDA-5), and protein kinase R (PKR). Our single-cell analysis reveals that viral replication requires a supra-unitary viral genome input, significantly more than one, which we define as the virion input threshold for replication (VITREP). This threshold varies depending on viruses and cell types, independently of viral protein synthesis. Through mathematical modeling and experimental testing, we uncover that supra-unitary viral genome quantities activate negative feedback regulators (NFR) of CyVSP, including death-associated protein kinase 1 (DAPK1), Rio kinase 3 (RIOK3), and protein phosphatase 2 regulatory subunit alpha (PPP2R2A), that suppress innate immune responses and allow replication. We validate key predictions of our model, namely that downregulating NFR reduces replication, whereas upregulating NFR or coinfecting cells promotes replication. Together, these findings reveal a fundamental mechanism governing viral infectivity and tissue tropism.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281652","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 : 2026-10-29Epub Date: 2026-09-01DOI: 10.1016/j.cell.2026.08.007
Yuda Chen, Klaus Yserentant, Kibeom Hong, Kehan Chen, Yiming Kuang, Robert S Picardo, Arghya Bhowmick, Arthur Charles-Orszag, Samuel J Lord, Lei Lu, Kaipeng Hou, Samuel I Mann, Sagar Bhattacharya, Maggie Horst, Jonathan B Grimm, Luke D Lavis, R Dyche Mullins, William F DeGrado, Bo Huang
{"title":"De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles.","authors":"Yuda Chen, Klaus Yserentant, Kibeom Hong, Kehan Chen, Yiming Kuang, Robert S Picardo, Arghya Bhowmick, Arthur Charles-Orszag, Samuel J Lord, Lei Lu, Kaipeng Hou, Samuel I Mann, Sagar Bhattacharya, Maggie Horst, Jonathan B Grimm, Luke D Lavis, R Dyche Mullins, William F DeGrado, Bo Huang","doi":"10.1016/j.cell.2026.08.007","DOIUrl":"10.1016/j.cell.2026.08.007","url":null,"abstract":"<p><p>Fluorescent imaging in live cells is a cornerstone of life sciences. While natural fluorescent proteins have been engineered to enhance individual features, no existing tag combines ideal properties into a single system: high brightness, reversible binding, compact size, and stability across diverse conditions. Here, we achieve this through de novo design of rhodamine binders (Rhobin). To harness the broad repertoire of rhodamine fluorophores, we developed a generalizable design strategy for a pan-rhodamine binder compatible with diverse wavelengths and applications. Rhobin enables live- and fixed-cell imaging of various subcellular targets in mammalian cells, showing brightness surpassing existing tags. Its reversible fluorophore binding supports super-resolution stimulated emission depletion (STED) and live-cell single-molecule imaging for extended durations compared with HaloTag. Beyond conventional systems, Rhobin enables live imaging of the extremophile Sulfolobus acidocaldarius at 75°C, previously inaccessible with current tags. Together, these results establish Rhobin as a versatile platform for next-generation imaging and biosensor design.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"7228-7242.e10"},"PeriodicalIF":45.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872785","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 : 2026-10-29DOI: 10.1016/j.cell.2026.09.019
Peer Bork,Chris Bowler,Leho Tedersoo,Michael Kuhn,TREC Consortium Coordinators,Samuel Abiven,Colomban de Vargas,Paola Y. Bertucci
{"title":"Toward planetary microbial systems biology","authors":"Peer Bork,Chris Bowler,Leho Tedersoo,Michael Kuhn,TREC Consortium Coordinators,Samuel Abiven,Colomban de Vargas,Paola Y. Bertucci","doi":"10.1016/j.cell.2026.09.019","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.019","url":null,"abstract":"Microorganisms underpin Earth’s biosphere, sustaining life, shaping biogeochemical cycles, and maintaining ecosystem stability. In an era of scientific and geopolitical fragmentation, we advocate for a \"planetary microbial systems biology\" (PMSB) framework to uncover the mechanisms and organizational principles governing Earth’s interconnected microbial systems across scales of matter, space, and time and in relation to underlying natural and anthropogenic drivers. PMSB combines molecular and cellular technologies, multi-omics data, artificial intelligence (AI), and integrated transdisciplinary research across ecosystems. By federating open data and combining field observations, experimentation, and modeling, PMSB enables predictive understanding of microbiome dynamics across planetary scales, thus filling a critical knowledge gap in our understanding of the co-evolution of life and the Earth-system.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"15 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281653","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":"Genetic coupling of floral rewards and signals underlies pollinator attraction","authors":"Feng-Quan Tan,Filip Slavkovic,Miao Zhang,Gabrièle Adam,Christelle Troadec,Zheng-Hua Jiang,Marion Verdenaud,Hadi Shirazi Parsa,Delphine Cuzzi,Xiaojuan Liu,Xiaoyuan Li,Ravi Sureshbhai Devani,Yuhang Yan,Qinghe Chen,Ying Huang,Nicolas Morison,Siqi Zhang,Fabien Marcel,Francoise Gilard,Bertrand Gakiere,David Latrasse,Moussa Benhamed,Julie Carcaud,Jean-Christophe Sandoz,Bernard Vaissiere,Adnane Boualem,Catherine Dogimont,Abdelhafid Bendahmane","doi":"10.1016/j.cell.2026.10.005","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.005","url":null,"abstract":"Animal pollinators underpin biodiversity and global agriculture, yet the molecular mechanisms that coordinate floral rewards and signals to attract pollinators remain poorly understood. Through phenotyping melon genetic diversity, we identified nectarless1 (nls1), encoding the YABBY-family transcription factor YABBY5 (YAB5), as a central integrator of pollinator-attracting traits. YAB5 interacts with CRABS CLAW (CRC) during nectary initiation to specify nectary identity by repressing alternative floral organ fates. As flowers mature, YAB5 directly activates 4-α-glucanotransferase 2 (DPE2) to promote starch remobilization required for nectar secretion and promotes petal growth and flower opening. In petals, YAB5 directly engages an MYB111-dependent flavonoid pathway that generates UV nectar guides, while indirectly influencing floral volatile emission. Disrupting YAB5, DPE2, or MYB111 reduces pollinator visitation. Together, these findings reveal how a developmental regulator couples organ specification with organ-specific metabolic programs to synchronize floral rewards and signals at anthesis.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"17 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281657","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}