Cell最新文献

{"title":"COP1 is a temperature-responsive switch in Arabidopsis","authors":"Wei Zeng,Laura Lamelas,Domenico Scaramozzino,Zhuo Angel Chen,Juri Rappsilber,Shuqin Xue,Katja E. Jaeger,Laura Orellana,Arun Sampathkumar,Philip A. Wigge","doi":"10.1016/j.cell.2026.10.036","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.036","url":null,"abstract":"Temperature is molecular motion, but how living systems sense this is poorly understood. Many responses in plants integrate light and temperature signals, for example, via light receptors and the circadian clock. CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) regulates light signaling and is necessary for responding to temperature. We show that COP1 acts as a temperature-dependent switch, becoming activated by a warm temperature-induced conformational change. An intramolecular Val-Pro (VP) motif binds to the active site of COP1 at low temperatures, preventing substrate docking. At warmer temperatures, the VP motif becomes detached, enabling client proteins to bind and be degraded. This discovery explains how plants are able to obtain a precise readout of temperature within a given climate range. Altering the binding of the VP motif is sufficient to adjust the temperature range within which the plant responds. This helps us understand how plants are able to adapt to different climates.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"14 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149374674","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":"Nicotianamine-driven nickel transport to sink organs underpins maize productivity","authors":"Zhen-Fei Chao,Yuanyuan Chen,Jia-Chen Wu,Ya-Ling Wang,Yingjie Xiao,Yong Peng,Lu-Yu Fan,Xiaqing Wang,Mei-Ling Han,Hai-Jun Liu,Nicolaus von Wirén,Jianbing Yan,Dai-Yin Chao","doi":"10.1016/j.cell.2026.10.035","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.035","url":null,"abstract":"Nickel (Ni), the last essential trace element identified in plants, has long been enigmatic regarding the genetic basis underlying its homeostasis and its agricultural significance. Using genome-wide association analysis, we identified ZmNAET1 as a key transporter controlling Ni allocation to seeds. Mechanistically, ZmNAET1 mediates nicotianamine secretion and enables nicotianamine-dependent phloem loading of Ni in nodes and subsequent Ni translocation into sink organs. Mutants lacking ZmNAET1 exhibit significant yield penalties, decreased seed germination velocity, and drastically shortened seed longevity. In an irreplaceable role, supplemented Ni fully rescued seed germination and proper vegetative development of the mutants. We show that NAET1-dependent delivery of Ni to urease is essential for amino acid turnover in developing sink organs, revealing an unappreciated role of Ni in yield formation of graminaceous plants. This study uncovers an underestimated requirement for nicotianamine and Ni and opens a new research avenue toward optimizing micronutrient provision for cereal crop productivity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149374672","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":"Reconstructing developmental and disease progression with sample-level embeddings","authors":"Longda Jiang,Zhixin Cyrillus Tan,Isabella N. Grabski,Yuhan Hao,Nathan Nakatsuka,Sourav Sarkar,Anagha Shenoy,Rahul Satija","doi":"10.1016/j.cell.2026.10.018","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.018","url":null,"abstract":"Single-cell genomics is transformative for characterizing cellular heterogeneity, but many biological questions require comparing samples rather than individual cells. Typical analyses compare “case” and “control” groups, ignoring sample-level variation within them. Here, we present scSLIDE (single-cell sample-level inference using density estimation), a framework that transforms each sample’s single-cell data into a compact profile describing where its cells are distributed in high-dimensional space. By comparing these density profiles, scSLIDE calculates embeddings to characterize variation across samples. We implement scSLIDE in version 6 of our Seurat package and apply it to COVID-19 infection, Alzheimer’s disease, and zebrafish embryogenesis. scSLIDE reveals patient subgroups, reconstructs disease trajectories, and identifies coordinated cellular programs across samples. We discover separable axes of infection and severity, a trajectory of Alzheimer’s progression, and embryonic “pseudostages” that vary across and within time points. Our results demonstrate how case-control analyses collapse rich biological variation into binary labels and how sample-level embedding represents a powerful analytical alternative.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"21 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149367752","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":"CRISPR mutagenesis of the MYC locus reveals a druggable ultraconserved RNA element.","authors":"Peiguo Shi, Feiyue Yang, Tala Fnu, Wesley Huang, Linqing Xing, Shah Alam, Wangyang Dai, Alexis O Aparicio, Colin H Kalicki, Aditi Trehan, Michael R Murphy, Esther R Rotlevi, Prajish Iyer, Lili Wang, Sara Zaccara, Muredach P Reilly, Ya Cheng Liao, Chaolin Zhang, Jianwen Que, Xuebing Wu","doi":"10.1016/j.cell.2026.10.002","DOIUrl":"10.1016/j.cell.2026.10.002","url":null,"abstract":"<p><p>Noncoding sequences comprise most of the human genome; however, their functional significance remains largely elusive. Using CRISPR tiling mutagenesis with near-PAMless, high-fidelity SpRY-Cas9, we mapped the fitness landscape of an entire human gene, the 10-kb MYC locus, at base-pair resolution. This unbiased interrogation revealed that 67% of functionally essential base pairs are noncoding. Essential noncoding base pairs are under strong constraint in the human population but show limited evolutionary conservation across species. Within this landscape, we identified an ultraconserved noncoding RNA element in the 3' untranslated region (UTR) that promotes perinuclear localization of MYC mRNA and nuclear localization of MYC protein through interaction with hnRNP L. Steric-blocking antisense oligonucleotides (ASOs) targeting this element selectively eliminate diverse MYC-dependent cancer cells and inhibit growth of patient-derived tumor organoids. Together, these findings establish noncoding sequences as major carriers of functional genetic information and identify a therapeutically actionable RNA element whose targeting disrupts MYC-driven cancer.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":45.1,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13739239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332604","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":"Industrialization drives convergent microbiome and host physiological shifts in the human metaorganism","authors":"Mathilde Poyet,Malte Rühlemann,Ana P. Schaan,Yue Ma,Lucas Moitinho-Silva,Eike M. Wacker,Hannah Jebens,Lucas Patel,Le Thanh Tu Nguyen,Alexis Zimmer,Damian Plichta,Daniel McDonald,Christine Stevens,Adwoa Agyei,Mary Y. Afihene,Shadrack O. Asibey,Yaw A. Awuku,Aida S. Badiane,Chris Corzett,Awa Deme,Manuel Dominguez-Rodrigo,Amoako Duah,Alain Fezeu,Alain Froment,Sean Gibbons,Catherine Girard,Jeff Hooker,Fatimah Ibrahim,Deborah Iqaluk,Vanessa Juimo,Pinja Kettunen,Sophie Lafosse,Ernest Lango-Yaya,Soo C. Lee,Jenni Lehtimäki,Yvonne A.L. Lim,Audax Mabulla,Varocha Mahachai,Rihlat S. Mohamed,Katya Moniz,Ivan E. Mwikarago,Yvonne A. Nartey,Daouda Ndiaye,Mary Noel,Charles Onyekwere,Tan M. Pin,Amelie Plymoth,Lewis Roberts,Lasse Ruokolainen,John Rusine,Laure Segurel,B. Jesse Shapiro,Shani Sigwazi,Ainara Sistiaga,Kenneth Valles,Tommi Vatanen,Ratha-korn Vilaichone,Philip Rosenstiel,John Baines,Andre Franke,David Ellinghaus,Rob Knight,Mark Daly,Ramnik J. Xavier,Eric J. Alm,Mathieu Groussin","doi":"10.1016/j.cell.2026.10.016","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.016","url":null,"abstract":"Understanding how industrialization reshapes the human metaorganism requires integrating microbiome ecology with host physiology across globally diverse populations. Here, we generate multivariate data from the Global Microbiome Conservancy cohort, including gut microbiome, immunoglobulin A (IgA) sequencing, host genotyping, diet, lifestyle, and fecal biomarker profiles, to investigate host-microbiome interactions across gradients of industrialization and geography. We show that industrialization is associated with homogenized microbial compositions, reduced microbial diversity, and lower community stability, independent of host confounders. We further show that industrialization is linked to elevated markers of gut stress, increased IgA secretion, and altered patterns of IgA-bacteria interactions. Finally, we show that microbiome-based disease predictors trained on industrialized populations are uninformative in less industrialized cohorts, highlighting limited cross-population transferability. Together, our results reveal coordinated restructuring of the microbial ecosystem and host physiology and emphasize the need for inclusive, globally representative data to improve translational microbiome applications across diverse human populations.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"23 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149304872","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":"TECR palmitoylation triggers a necrotic cell death program driving acute liver injury","authors":"Xiaoyan Ru,Xinran Li,Zhili Wu,Xinhua Ren,Yu Zong,Yazhong Cui,Yuhua Li,Zhangcheng Ding,Xiaodong Wang,Ze Zhang","doi":"10.1016/j.cell.2026.10.011","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.011","url":null,"abstract":"Acute liver injury caused by drug toxicity or immune activation remains a major clinical challenge with limited mechanistic understanding and few effective therapies. Here, we identify a previously unrecognized form of regulated cell death driven by palmitoylation of the endoplasmic reticulum (ER)-resident enzyme trans-2,3-enoyl-coenzyme A (CoA) reductase (TECR). We show that multi-site palmitoylation of TECR, redundantly catalyzed by the palmitoyl acyltransferases ZDHHC5 and ZDHHC2 and dynamically reversed by the depalmitoylase ABHD10, activates PERK-dependent ER stress signaling to trigger cell death. This cell death pathway is a TECR-dependent, palmitoylation-induced, ER stress-mediated necrotic cell death program (TPNCD). TPNCD contributes to liver injury in mouse models of acetaminophen- and concanavalin A-induced hepatotoxicity and is attenuated by hepatocyte-specific TECR ablation or by pharmacological inhibition of palmitoylation or ER stress signaling. Together, these findings establish TPNCD as a distinct, necrotic cell death pathway underlying acute liver injury and highlight new therapeutic entry points for hepatoprotection.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149304896","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":"Convergent genomic evolution of human gut bacteria along an industrialization gradient","authors":"Malte Rühlemann,Yue Ma,Lénárd L. Szánthó,Silvio Waschina,Lucas Moitinho-Silva,Laura C. Mews,Joan Faus-Camarena,Hannah Jebens,John Costa,Vanessa Juimo,Alain Fezeu,Adwoa Agyei,Mary Y. Afihene,Shadrack O. Asibey,Yaw A. Awuku,Amoako Duah,Yvonne A. Nartey,Fatimah Ibrahim,Yvonne A.L. Lim,Maw Pin Tan,Charles Onyekwere,John Rusine,Ivan E. Mwikarago,John Baines,Andre Franke,Gergely J. Szöllősi,Ramnik J. Xavier,Eric J. Alm,Mathieu Groussin,Mathilde Poyet","doi":"10.1016/j.cell.2026.10.014","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.014","url":null,"abstract":"Whether human-associated environments drive adaptive genome evolution in gut commensal bacteria remains largely unknown. Here, we investigate how genomic adaptation in gut bacteria differs between industrialized and non-industrialized human populations. We generated a collection of isolate genomes spanning diverse host geographies, lifestyles, species, and strains. We first found that, compared with metagenome-assembled genomes (MAGs), paired isolate genomes recover more functional elements and signals of horizontal gene transfer (HGT). Leveraging isolate genomes from multiple species, we find that strains from industrialized hosts experience an expansion of proteome size and harbor greater pangenome fluidity, driven by recent HGT events. Gene- and variant-level analyses reveal convergent patterns of lifestyle-specific adaptation in functions that are critical for ecological adaptation, such as the stress response, cell-envelope remodeling, and central metabolism. Our results demonstrate that industrialization drives convergent genome evolution in gut bacteria, providing a framework for understanding the mechanisms of microbial adaptation to rapidly changing human environments.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"85 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149304871","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":"Subsistence transition preceded population turnover in the eastern Colombian Andes","authors":"Kendra Sirak,Miguel Delgado,Angélica Viviana Triana Vega,Sebastián Rivas,Pedro Argüello,Ana María Boada,Javier Rivera-Sandoval,Germán Peña,Carl Langebaek,Juan Pablo Ospina,Sonia Archila,Saúl Alberto Torres Orjuela,Martha Beatriz Mejía Cano,Freddy Rodríguez Saza,Alison Barton,Kim Callan,Elizabeth Curtis,Trudi Frost,Lora Iliev,Aisling Kearns,Jack Kellogg,Ann Marie Lawson,Lijun Qiu,J. Noah Workman,Matthew Mah,Mariam Nawaz,Gregory Soos,Alexander Cherkinsky,Carla S. Hadden,Keith M. Prufer,Swapan Mallick,Nadin Rohland,Lars Fehren-Schmitz,David Reich","doi":"10.1016/j.cell.2026.10.010","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.010","url":null,"abstract":"The Altiplano Cundiboyacense in the eastern Colombian Andes preserves one of the Americas’ most continuous archaeological sequences, recording cultural and demographic change. We generated genome-wide data from 212 individuals spanning over 7,000 years, including early-middle and middle Holocene hunter-gatherers, initial late Holocene groups with mixed economies and the earliest isotopic evidence of maize consumption, and increasingly sedentary Herrera and Muisca populations. Individuals predating the Herrera Period form a lineage that persisted for five millennia, structured by drift in small groups without external gene flow. Two individuals dating ∼2,800 years before present (BP) retain autochthonous ancestry while showing isotopic signatures consistent with maize consumption, decoupling subsistence change from population replacement. The emergence of Herrera culture ∼2,200 BP coincided with a sharp genetic break by ∼2,000 BP, which reflects migration by people descended from admixture ∼4,000 BP between groups with Chibchan- and Amazonian-Andean-related ancestries. Herrera and Muisca Period individuals show north-south genetic substructure paralleling archaeological differentiation.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"28 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149304873","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":"Fatty acid desaturation controls cellular fate decisions between senescence and ferroptosis","authors":"Chisaka Kuehnemann,Samantha T. Jezak,Bronwyn A. Mogck,Niharika Kura,Rushmeen Tariq,Yuheng Che,Maija Vaittinen,Ioannis Siokas,Sharvari Deshpande,Carlyn Guthrie,Xuejuan Tan,Eliezer Aimontche,Aleksandra Aljakna Kahn,Peter Reifsnyder,Gung Lee,Amene Majidipur,Andrew H. Kung,Qiaoling Wang,Diana Jurk,Tong Zheng,Andrew S. Greenberg,Xiang-Dong Wang,Koji Kitazawa,Gregory Dolnikowsi,Yong Cheng,Nirupa R. Matthan,Arvind Ramanthan,Jennifer Lee,Daniel Roh,Howard H. Chen,Jussi Pihlajamaki,Ron Korstanje,Christopher D. Wiley","doi":"10.1016/j.cell.2026.09.036","DOIUrl":"https://doi.org/10.1016/j.cell.2026.09.036","url":null,"abstract":"When subject to damage or stress, cells develop responses in order to maintain tissue homeostasis. Two such responses are ferroptosis and cellular senescence, but how cells decide between these outcomes remains unclear. Here, we show that senescent cells increase import and membrane levels of multiple polyunsaturated fatty acids (PUFAs), but a specific intermediate PUFA, dihomo-gamma-linolenic acid (DGLA, 20:3 ω -6), is reduced. Exogenous repletion of DGLA instead results in cell death by ferroptosis. Senescent cells manifest additional features associated with ferroptosis, including labile iron and expression of lipoxygenases as well as low-level membrane peroxidation. Oral DGLA supplementation lowers markers of senescence in aged mice and improves age-related functional outcomes. Finally, obese humans with lowered DGLA desaturation rates have lower markers of adipose tissue senescence. Together, our data implicate shifts in PUFA metabolism as a driver of decisions between senescence and ferroptosis.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"18 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149304869","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":"Age-dependent structural evolution of a functional amyloid contributes to memory impairment in Drosophila.","authors":"Songxian Ou, Pablo Adrian Guillen-Poza, Kevin Kan-Shing Ng, Lezhi Xu, Bin Yang Cheng, Yangyang Yi, Lok Yin Ho, Angela Franco-Fernández, Peerzada Shariq Shaheen Khaki, Mayur Mukhi, Kai Chit Cheung, Rakesh Sharma, Javier Oroz, Yukinori Hirano, Ruben Hervas","doi":"10.1016/j.cell.2026.10.009","DOIUrl":"https://doi.org/10.1016/j.cell.2026.10.009","url":null,"abstract":"<p><p>Cryogenic electron microscopy has revealed endpoint structures of ex vivo amyloid filaments, but how amyloids assemble and evolve in living organisms-and how these transitions affect physiology-remains poorly understood. Here, we map the age-dependent structural landscape of Orb2 amyloid, a synaptic translation regulator required for long-term memory, across the adult lifespan of Drosophila melanogaster. By determining multiple Orb2 amyloid structures, we uncover a dynamic, age-linked progression of amyloid states. Translation-promoting assemblies predominate early in life, whereas aging shifts the Orb2 amyloid ensemble toward structurally distinct, destabilization-resistant assemblies with reduced translational activity, coinciding with memory impairment. Manipulating memory-related chaperones in the brain shifts Orb2 toward youthful, translation-promoting states and improves memory in old flies; conversely, shifting Orb2 toward aged-like, translation-deficient states in young adults is associated with premature memory impairment. These findings define an in vivo trajectory of amyloid evolution and link amyloid structural dynamics to synaptic translation and memory.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":45.1,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294986","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}