{"title":"Microbial ecosystems and ecological driving forces in the deepest ocean sediments","authors":"Xiang Xiao, Weishu Zhao, Zewei Song, Qi Qi, Bo Wang, Jiahui Zhu, James Lin, Jing Wang, Aoran Hu, Shanshan Huang, Yinzhao Wang, Jianwei Chen, Chao Fang, Qianyue Ji, Nannan Zhang, Liang Meng, Xiaofeng Wei, Chuanxu Chen, Shanya Cai, Shun Chen, Shanshan Liu","doi":"10.1016/j.cell.2024.12.036","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.036","url":null,"abstract":"Systematic exploration of the hadal zone, Earth’s deepest oceanic realm, has historically faced technical limitations. Here, we collected 1,648 sediment samples at 6–11 km in the Mariana Trench, Yap Trench, and Philippine Basin for the Mariana Trench Environment and Ecology Research (MEER) project. Metagenomic and 16S rRNA gene amplicon sequencing generated the 92-Tbp MEER dataset, comprising 7,564 species (89.4% unreported), indicating high taxonomic novelty. Unlike in reported environments, neutral drift played a minimal role, while homogeneous selection (HoS, 50.5%) and dispersal limitation (DL, 43.8%) emerged as dominant ecological drivers. HoS favored streamlined genomes with key functions for hadal adaptation, e.g., aromatic compound utilization (oligotrophic adaptation) and antioxidation (high-pressure adaptation). Conversely, DL promoted versatile metabolism with larger genomes. These findings indicated that environmental factors drive the high taxonomic novelty in the hadal zone, advancing our understanding of the ecological mechanisms governing microbial ecosystems in such an extreme oceanic environment.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560866","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 : 2025-03-06DOI: 10.1016/j.cell.2025.01.038
Sondra Turjeman, Tommaso Rozera, Eran Elinav, Gianluca Ianiro, Omry Koren
{"title":"From big data and experimental models to clinical trials: Iterative strategies in microbiome research","authors":"Sondra Turjeman, Tommaso Rozera, Eran Elinav, Gianluca Ianiro, Omry Koren","doi":"10.1016/j.cell.2025.01.038","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.038","url":null,"abstract":"Microbiome research has expanded significantly in the last two decades, yet translating findings into clinical applications remains challenging. This perspective discusses the persistent issue of correlational studies in microbiome research and proposes an iterative method leveraging <em>in silico</em>, <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> studies toward successful preclinical and clinical trials. The evolution of research methodologies, including the shift from small cohort studies to large-scale, multi-cohort, and even “meta-cohort” analyses, has been facilitated by advancements in sequencing technologies, providing researchers with tools to examine multiple health phenotypes within a single study. The integration of multi-omics approaches—such as metagenomics, metatranscriptomics, metaproteomics, and metabolomics—provides a comprehensive understanding of host-microbe interactions and serves as a robust hypothesis generator for downstream <em>in vitro</em> and <em>in vivo</em> research. These hypotheses must then be rigorously tested, first with proof-of-concept experiments to clarify the causative effects of the microbiota, and then with the goal of deep mechanistic understanding. Only following these two phases can preclinical studies be conducted with the goal of translation into the clinic. We highlight the importance of combining traditional microbiological techniques with big-data approaches, underscoring the necessity of iterative experiments in diverse model systems to enhance the translational potential of microbiome research.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"2 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560867","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 : 2025-03-05DOI: 10.1016/j.cell.2025.02.005
Pamela E. Rios Coronado, Jiayan Zhou, Xiaochen Fan, Daniela Zanetti, Jeffrey A. Naftaly, Pratima Prabala, Azalia M. Martínez Jaimes, Elie N. Farah, Soumya Kundu, Salil S. Deshpande, Ivy Evergreen, Pik Fang Kho, Qixuan Ma, Austin T. Hilliard, Sarah Abramowitz, Saiju Pyarajan, Daniel Dochtermann, Scott M. Damrauer, Kyong-Mi Chang, Themistocles L. Assimes
{"title":"CXCL12 drives natural variation in coronary artery anatomy across diverse populations","authors":"Pamela E. Rios Coronado, Jiayan Zhou, Xiaochen Fan, Daniela Zanetti, Jeffrey A. Naftaly, Pratima Prabala, Azalia M. Martínez Jaimes, Elie N. Farah, Soumya Kundu, Salil S. Deshpande, Ivy Evergreen, Pik Fang Kho, Qixuan Ma, Austin T. Hilliard, Sarah Abramowitz, Saiju Pyarajan, Daniel Dochtermann, Scott M. Damrauer, Kyong-Mi Chang, Themistocles L. Assimes","doi":"10.1016/j.cell.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.cell.2025.02.005","url":null,"abstract":"Coronary arteries have a specific branching pattern crucial for oxygenating heart muscle. Among humans, there is natural variation in coronary anatomy with respect to perfusion of the inferior/posterior left heart, which can branch from either the right arterial tree, the left, or both—a phenotype known as coronary dominance. Using angiographic data for >60,000 US veterans of diverse ancestry, we conducted a genome-wide association study of coronary dominance, revealing moderate heritability and identifying ten significant loci. The strongest association occurred near <em>CXCL12</em> in both European- and African-ancestry cohorts, with downstream analyses implicating effects on <em>CXCL12</em> expression. We show that <em>CXCL12</em> is expressed in human fetal hearts at the time dominance is established. Reducing <em>Cxcl12</em> in mice altered coronary dominance and caused septal arteries to develop away from <em>Cxcl12</em> expression domains. These findings indicate that <em>CXCL12</em> patterns human coronary arteries, paving the way for “medical revascularization” through targeting developmental pathways.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"30 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546572","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 : 2025-03-05DOI: 10.1016/j.cell.2025.02.003
Sven Klumpe, Kirsten A. Senti, Florian Beck, Jenny Sachweh, Bernhard Hampoelz, Paolo Ronchi, Viola Oorschot, Marlene Brandstetter, Assa Yeroslaviz, John A.G. Briggs, Julius Brennecke, Martin Beck, Jürgen M. Plitzko
{"title":"In-cell structure and snapshots of copia retrotransposons in intact tissue by cryoelectron tomography","authors":"Sven Klumpe, Kirsten A. Senti, Florian Beck, Jenny Sachweh, Bernhard Hampoelz, Paolo Ronchi, Viola Oorschot, Marlene Brandstetter, Assa Yeroslaviz, John A.G. Briggs, Julius Brennecke, Martin Beck, Jürgen M. Plitzko","doi":"10.1016/j.cell.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.cell.2025.02.003","url":null,"abstract":"Long terminal repeat (LTR) retrotransposons belong to the transposable elements (TEs), autonomously replicating genetic elements that integrate into the host’s genome. Among animals, <em>Drosophila melanogaster</em> serves as an important model organism for TE research and contains several LTR retrotransposons, including the Ty1-<em>copia</em> family, which is evolutionarily related to retroviruses and forms virus-like particles (VLPs). In this study, we use cryo-focused ion beam (FIB) milling and lift-out approaches to visualize <em>copia</em> VLPs in ovarian cells and intact egg chambers, resolving the <em>in situ copia</em> capsid structure to 7.7 Å resolution by cryoelectron tomography (cryo-ET). Although cytoplasmic <em>copia</em> VLPs vary in size, nuclear VLPs are homogeneous and form densely packed clusters, supporting a model in which nuclear import acts as a size selector. Analyzing flies deficient in the TE-suppressing PIWI-interacting RNA (piRNA) pathway, we observe <em>copia</em>’s translocation into the nucleus during spermatogenesis. Our findings provide insights into the replication cycle and cellular structural biology of an active LTR retrotransposon.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"13 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546571","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 : 2025-03-04DOI: 10.1016/j.cell.2025.01.044
Ugne Klibaite, Tianqing Li, Diego Aldarondo, Jumana F. Akoad, Bence P. Ölveczky, Timothy W. Dunn
{"title":"Mapping the landscape of social behavior","authors":"Ugne Klibaite, Tianqing Li, Diego Aldarondo, Jumana F. Akoad, Bence P. Ölveczky, Timothy W. Dunn","doi":"10.1016/j.cell.2025.01.044","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.044","url":null,"abstract":"Social interaction is integral to animal behavior. However, lacking tools to describe it in quantitative and rigorous ways has limited our understanding of its structure, underlying principles, and the neuropsychiatric disorders, like autism, that perturb it. Here, we present a technique for high-resolution 3D tracking of postural dynamics and social touch in freely interacting animals, solving the challenging subject occlusion and part-assignment problems using 3D geometric reasoning, graph neural networks, and semi-supervised learning. We collected over 110 million 3D pose samples in interacting rats and mice, including seven monogenic autism rat lines. Using a multi-scale embedding approach, we identified a rich landscape of stereotyped actions, interactions, synchrony, and body contacts. This high-resolution phenotyping revealed a spectrum of changes in autism models and in response to amphetamine not resolved by conventional measurements. Our framework and large library of interactions will facilitate studies of social behaviors and their neurobiological underpinnings.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"37 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538717","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 : 2025-03-03DOI: 10.1016/j.cell.2025.02.002
Zhiguang Chang, Xuan Guo, Xuefei Li, Yan Wang, Zhongsheng Zang, Siyu Pei, Weiqi Lu, Yang Li, Jian-Dong Huang, Yichuan Xiao, Chenli Liu
{"title":"Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization","authors":"Zhiguang Chang, Xuan Guo, Xuefei Li, Yan Wang, Zhongsheng Zang, Siyu Pei, Weiqi Lu, Yang Li, Jian-Dong Huang, Yichuan Xiao, Chenli Liu","doi":"10.1016/j.cell.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.cell.2025.02.002","url":null,"abstract":"Bacterial immunotherapy holds promising cancer-fighting potential. However, unlocking its power requires a mechanistic understanding of how bacteria both evade antimicrobial immune defenses and stimulate anti-tumor immune responses within the tumor microenvironment (TME). Here, by harnessing an engineered <em>Salmonella enterica</em> strain with this dual proficiency, we unveil an underlying singular mechanism. Specifically, the hysteretic nonlinearity of interleukin-10 receptor (IL-10R) expression drives tumor-infiltrated immune cells into a tumor-specific IL-10R<sup>hi</sup> state. Bacteria leverage this to enhance tumor-associated macrophages producing IL-10, evade phagocytosis by tumor-associated neutrophils, and coincidently expand and stimulate the preexisting exhausted tumor-resident CD8<sup>+</sup> T cells. This effective combination eliminates tumors, prevents recurrence, and inhibits metastasis across multiple tumor types. Analysis of human samples suggests that the IL-10R<sup>hi</sup> state might be a ubiquitous trait across human tumor types. Our study unveils the unsolved mechanism behind bacterial immunotherapy’s dual challenge in solid tumors and provides a framework for intratumoral immunomodulation.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532370","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 : 2025-02-28DOI: 10.1016/j.cell.2025.02.024
Tom Maniatis
{"title":"Safeguarding the future of biomedical science in the United States","authors":"Tom Maniatis","doi":"10.1016/j.cell.2025.02.024","DOIUrl":"https://doi.org/10.1016/j.cell.2025.02.024","url":null,"abstract":"NIH’s abrupt decision to cap indirect cost reimbursement at 15% threatens the critical infrastructure supporting groundbreaking biomedical research in the United States. This policy jeopardizes America’s global leadership in science and medicine. Urgent action is needed to advocate for its immediate and permanent reversal to protect the future of science.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"33 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526494","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 : 2025-02-28DOI: 10.1016/j.cell.2025.01.046
Qinqin Jiang, David A. Braun, Karl R. Clauser, Vijyendra Ramesh, Nitin H. Shirole, Joseph E. Duke-Cohan, Nancy Nabilsi, Nicholas J. Kramer, Cleo Forman, Isabelle E. Lippincott, Susan Klaeger, Kshiti M. Phulphagar, Vipheaviny Chea, Nawoo Kim, Allison P. Vanasse, Eddy Saad, Teagan Parsons, Melissa Carr-Reynolds, Isabel Carulli, Katarina Pinjusic, William G. Kaelin
{"title":"HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy","authors":"Qinqin Jiang, David A. Braun, Karl R. Clauser, Vijyendra Ramesh, Nitin H. Shirole, Joseph E. Duke-Cohan, Nancy Nabilsi, Nicholas J. Kramer, Cleo Forman, Isabelle E. Lippincott, Susan Klaeger, Kshiti M. Phulphagar, Vipheaviny Chea, Nawoo Kim, Allison P. Vanasse, Eddy Saad, Teagan Parsons, Melissa Carr-Reynolds, Isabel Carulli, Katarina Pinjusic, William G. Kaelin","doi":"10.1016/j.cell.2025.01.046","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.046","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC), despite having a low mutational burden, is considered immunogenic because it occasionally undergoes spontaneous regressions and often responds to immunotherapies. The signature lesion in ccRCC is inactivation of the <em>VHL</em> tumor suppressor gene and consequent upregulation of the HIF transcription factor. An earlier case report described a ccRCC patient who was cured by an allogeneic stem cell transplant and later found to have donor-derived T cells that recognized a ccRCC-specific peptide encoded by a HIF-responsive endogenous retrovirus (ERV), ERVE-4. We report that ERVE-4 is one of many ERVs that are induced by HIF, translated into HLA-bound peptides in ccRCCs, and capable of generating antigen-specific T cell responses. Moreover, ERV expression can be induced in non-ccRCC tumors with clinical-grade HIF stabilizers. These findings have implications for leveraging ERVs for cancer immunotherapy.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"25 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517819","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 : 2025-02-28DOI: 10.1016/j.cell.2025.01.041
Maxime Beau, David J. Herzfeld, Francisco Naveros, Marie E. Hemelt, Federico D’Agostino, Marlies Oostland, Alvaro Sánchez-López, Young Yoon Chung, Michael Maibach, Stephen Kyranakis, Hannah N. Stabb, M. Gabriela Martínez Lopera, Agoston Lajko, Marie Zedler, Shogo Ohmae, Nathan J. Hall, Beverley A. Clark, Dana Cohen, Stephen G. Lisberger, Dimitar Kostadinov, Javier F. Medina
{"title":"A deep learning strategy to identify cell types across species from high-density extracellular recordings","authors":"Maxime Beau, David J. Herzfeld, Francisco Naveros, Marie E. Hemelt, Federico D’Agostino, Marlies Oostland, Alvaro Sánchez-López, Young Yoon Chung, Michael Maibach, Stephen Kyranakis, Hannah N. Stabb, M. Gabriela Martínez Lopera, Agoston Lajko, Marie Zedler, Shogo Ohmae, Nathan J. Hall, Beverley A. Clark, Dana Cohen, Stephen G. Lisberger, Dimitar Kostadinov, Javier F. Medina","doi":"10.1016/j.cell.2025.01.041","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.041","url":null,"abstract":"High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but fail to reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals and reveal the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetics and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep learning classifier that predicts cell types with greater than 95% accuracy based on the waveform, discharge statistics, and layer of the recorded neuron. The classifier’s predictions agree with expert classification on recordings using different probes, in different laboratories, from functionally distinct cerebellar regions, and across species. Our classifier extends the power of modern dynamical systems analyses by revealing the unique contributions of simultaneously recorded cell types during behavior.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"31 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517816","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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