CellPub Date : 2025-09-09DOI: 10.1016/j.cell.2025.08.018
José R. Penadés, Juraj Gottweis, Lingchen He, Jonasz B. Patkowski, Alexander Daryin, Wei-Hung Weng, Tao Tu, Anil Palepu, Artiom Myaskovsky, Annalisa Pawlosky, Vivek Natarajan, Alan Karthikesalingam, Tiago R.D. Costa
{"title":"AI mirrors experimental science to uncover a mechanism of gene transfer crucial to bacterial evolution","authors":"José R. Penadés, Juraj Gottweis, Lingchen He, Jonasz B. Patkowski, Alexander Daryin, Wei-Hung Weng, Tao Tu, Anil Palepu, Artiom Myaskovsky, Annalisa Pawlosky, Vivek Natarajan, Alan Karthikesalingam, Tiago R.D. Costa","doi":"10.1016/j.cell.2025.08.018","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.018","url":null,"abstract":"Artificial intelligence (AI) models have been proposed for hypothesis generation, but testing their ability to drive high-impact research is challenging since an AI-generated hypothesis can take decades to validate. Here, we challenge the ability of a recently developed large language model (LLM)-based platform, AI co-scientist, to generate high-level hypotheses by posing a question that took years to resolve experimentally but remained unpublished: how could capsid-forming phage-inducible chromosomal islands (cf-PICIs) spread across bacterial species? Remarkably, the AI co-scientist’s top-ranked hypothesis matched our experimentally confirmed mechanism: cf-PICIs hijack diverse phage tails to expand their host range. We critically assess its five highest-ranked hypotheses, showing that some opened new research avenues in our laboratories. We benchmark its performance against other LLMs and outline best practices for integrating AI into scientific discovery. Our findings suggest that AI can act not just as a tool but as a creative engine, accelerating discovery and reshaping how we generate and test scientific hypotheses.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"35 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017917","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 : 2025-09-05DOI: 10.1016/j.cell.2025.08.017
Victor S. Cortez, Sara Viragova, Satoshi Koga, Meizi Liu, Claire E. O’Leary, Roberto R. Ricardo-Gonzalez, Andrew W. Schroeder, Nathan Kochhar, Dedeepya Vaka, Dario Boffelli, Ophir D. Klein, Michael S. Diamond, Hong-Erh Liang, Richard M. Locksley
{"title":"IL-25-induced memory type 2 innate lymphoid cells enforce mucosal immunity","authors":"Victor S. Cortez, Sara Viragova, Satoshi Koga, Meizi Liu, Claire E. O’Leary, Roberto R. Ricardo-Gonzalez, Andrew W. Schroeder, Nathan Kochhar, Dedeepya Vaka, Dario Boffelli, Ophir D. Klein, Michael S. Diamond, Hong-Erh Liang, Richard M. Locksley","doi":"10.1016/j.cell.2025.08.017","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.017","url":null,"abstract":"Adaptation of intestinal helminths to vertebrates involved the evolution of strategies to attenuate host tissue damage to support parasite reproduction and dissemination of offspring to the environment. Helminths initiate the IL-25-mediated tuft cell-type 2 innate lymphoid cell (ILC2) circuit that enhances barrier protection of the host, although viable parasites can target and limit this pathway. We used IL-25 alone to create small intestinal adaptation, marked by anatomic and immunologic changes that persisted months after induction. Adaptation was associated with heightened resistance to barrier pathogens, including in the lung, and was enforced by transcriptionally and epigenetically modified effector-memory ILC2s distinct from those described by innate “training”; epithelial stem cells remained unaltered. Despite requiring IL-25 for induction, effector-memory ILC2s maintained an activated state in the absence of multiple alarmins and supported mucosal resilience while avoiding adverse sensitization to chronic inflammation, revealing a pathway for deploying innate immune cells to coordinate a distributed mucosal defense.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"24 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996042","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 : 2025-09-05DOI: 10.1016/j.cell.2025.08.015
Jeany Delafiori, Mohammed Shahraz, Andreas Eisenbarth, Volker Hilsenstein, Bernhard Drotleff, Alberto Bailoni, Bishoy Wadie, Måns Ekelöf, Alexander Mattausch, Theodore Alexandrov
{"title":"HT SpaceM: A high-throughput and reproducible method for small-molecule single-cell metabolomics","authors":"Jeany Delafiori, Mohammed Shahraz, Andreas Eisenbarth, Volker Hilsenstein, Bernhard Drotleff, Alberto Bailoni, Bishoy Wadie, Måns Ekelöf, Alexander Mattausch, Theodore Alexandrov","doi":"10.1016/j.cell.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.015","url":null,"abstract":"Single-cell metabolomics (SCM) promises to reveal metabolism in its complexity and heterogeneity, yet current methods struggle with detecting small-molecule metabolites, throughput, and reproducibility. Addressing these gaps, we developed HT SpaceM, a high-throughput SCM method combining cell preparation on custom glass slides, small-molecule matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MS), and batch processing. We propose a unified framework covering quality control, characterization, structural validation, and differential and functional analyses. Profiling HeLa and NIH3T3 cells, we detected 73 small-molecule metabolites validated by bulk liquid chromatography tandem MS (LC-MS/MS), achieving high reproducibility and single-cell resolution. Interrogating nine NCI-60 cancer cell lines and HeLa, we identified cell-type markers in subpopulations and metabolic hubs. Upon inhibiting glycolysis in HeLa cells, we observed emerging glucose-centered metabolic coordination and intra-condition heterogeneity. Overall, we demonstrate how HT SpaceM enables robust, large-scale SCM across over 140,000 cells from 132 samples and provide guidance on how to interpret metabolic insights beyond population averages.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"14 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996055","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 : 2025-09-04Epub Date: 2025-08-22DOI: 10.1016/j.cell.2025.08.009
Erin Huiting, Xueli Cao, Jie Ren, Januka S Athukoralage, Zhaorong Luo, Sukrit Silas, Na An, Héloïse Carion, Yu Zhou, James S Fraser, Yue Feng, Joseph Bondy-Denomy
{"title":"Bacteriophages inhibit and evade cGAS-like immune function in bacteria.","authors":"Erin Huiting, Xueli Cao, Jie Ren, Januka S Athukoralage, Zhaorong Luo, Sukrit Silas, Na An, Héloïse Carion, Yu Zhou, James S Fraser, Yue Feng, Joseph Bondy-Denomy","doi":"10.1016/j.cell.2025.08.009","DOIUrl":"10.1016/j.cell.2025.08.009","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"5118"},"PeriodicalIF":42.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944268","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 : 2025-09-04DOI: 10.1016/j.cell.2025.06.021
Matthias W. Hentze, Pia Sommerkamp, Venkatraman Ravi, Fátima Gebauer
{"title":"Rethinking RNA-binding proteins: Riboregulation challenges prevailing views","authors":"Matthias W. Hentze, Pia Sommerkamp, Venkatraman Ravi, Fátima Gebauer","doi":"10.1016/j.cell.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.021","url":null,"abstract":"RNA-binding proteins (RBPs) are best known as effectors along the entire gene expression pathway and as constituents of RNA-protein machines such as the ribosome and the spliceosome. Around 1,000 RBPs account for these functions in mammalian cells. The total number of RBPs has recently more than tripled to include many “well-known” proteins such as metabolic enzymes or membrane proteins, sparking debate about the biological relevance of their RNA binding. We examine the experimental basis underlying the dramatic expansion of the RBPome, consider arguments that challenge its relevance, and discuss recent data that describe new RBP and RNA functions. We suggest that the scope of interplay between RNA and proteins is underexplored and that riboregulation of proteins represents an emerging theme in cell biology and translational medicine.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987606","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 : 2025-09-04Epub Date: 2025-08-21DOI: 10.1016/j.cell.2025.08.010
Simon Haziza, Radosław Chrapkiewicz, Yanping Zhang, Vasily Kruzhilin, Jane Li, Jizhou Li, Geoffroy Delamare, Rachel Swanson, György Buzsáki, Madhuvanthi Kannan, Ganesh Vasan, Michael Z Lin, Hongkui Zeng, Tanya L Daigle, Mark J Schnitzer
{"title":"Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals.","authors":"Simon Haziza, Radosław Chrapkiewicz, Yanping Zhang, Vasily Kruzhilin, Jane Li, Jizhou Li, Geoffroy Delamare, Rachel Swanson, György Buzsáki, Madhuvanthi Kannan, Ganesh Vasan, Michael Z Lin, Hongkui Zeng, Tanya L Daigle, Mark J Schnitzer","doi":"10.1016/j.cell.2025.08.010","DOIUrl":"10.1016/j.cell.2025.08.010","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"5119"},"PeriodicalIF":42.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944206","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 : 2025-09-04DOI: 10.1016/j.cell.2025.08.012
Kaile Wang, Rui Ye, Shanshan Bai, Zhenna Xiao, Lei Yang, Jianzhuo Li, Chenling Tang, Emi Sei, Jinyu Peng, Anna K. Casasent, Steven H. Lin, Chandandeep Nagi, Alastair M. Thompson, Savitri Krishnamurthy, Nicholas E. Navin
{"title":"Coalescing single-cell genomes and transcriptomes to decode breast cancer progression","authors":"Kaile Wang, Rui Ye, Shanshan Bai, Zhenna Xiao, Lei Yang, Jianzhuo Li, Chenling Tang, Emi Sei, Jinyu Peng, Anna K. Casasent, Steven H. Lin, Chandandeep Nagi, Alastair M. Thompson, Savitri Krishnamurthy, Nicholas E. Navin","doi":"10.1016/j.cell.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.012","url":null,"abstract":"Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin. In contrast to bulk studies, wellDR-seq enabled the study of subclone-level gene-dosage relationships, which showed near-linear correlations in large chromosomal segments and extensive variation at the single-gene level. We identified dosage-sensitive and dosage-insensitive genes, including many breast cancer genes as well as sporadic copy-number aberrations in non-cancer cells. Overall, these data reveal complex relationships between copy number and gene expression in single cells, improving our understanding of breast cancer progression.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987623","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 : 2025-09-03DOI: 10.1016/j.cell.2025.08.013
Yujiao Han, Hirak Sarkar, Zhan Xu, Sereno Lopez-Darwin, Yong Wei, Xiang Hang, Fengshuo Liu, Kimberley Tran, Wei Wang, Jennifer M. Miller, Christina J. DeCoste, Dylan S. Blohm, Robert L. Satcher, Xiang H.-F. Zhang, Yibin Kang
{"title":"Tumors hijack macrophages for iron supply to promote bone metastasis and anemia","authors":"Yujiao Han, Hirak Sarkar, Zhan Xu, Sereno Lopez-Darwin, Yong Wei, Xiang Hang, Fengshuo Liu, Kimberley Tran, Wei Wang, Jennifer M. Miller, Christina J. DeCoste, Dylan S. Blohm, Robert L. Satcher, Xiang H.-F. Zhang, Yibin Kang","doi":"10.1016/j.cell.2025.08.013","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.013","url":null,"abstract":"Bone marrow is both a primary site for hematopoiesis and a fertile niche for metastasis. The mechanism of the common occurrence of anemia among patients with bone metastasis remains poorly understood. Here, we show that a specialized population of VCAM1<sup>+</sup>CD163<sup>+</sup>CCR3<sup>+</sup> macrophages, normally essential for erythropoiesis by transporting iron to erythroblasts, are highly enriched in the bone metastatic niche in mouse models. Tumor cells hijack these macrophages for iron supply, reducing iron availability for erythroblasts, impairing erythropoiesis, and contributing to anemia. Increased iron supply enables tumor cells to produce hemoglobin in response to hypoxia, mimicking erythroblasts. We identify macrophages with similar iron-transporting features in human bone metastases and show that elevated <em>HBB</em> expression correlates with increased risk of bone metastasis. These findings establish iron-transporting macrophages as an essential component of the metastatic bone niche, revealing a critical interplay between immune cells, metal metabolism, and tumor cell plasticity in driving metastasis and anemia.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930868","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 : 2025-09-03DOI: 10.1016/j.cell.2025.08.014
Ce Shi, Zifu Zhao, Yicheng Zhong, Ying Qiao, Lai Zhang, Fan Yang, Siyuan Li, Lulu Li, Lanjie Huang, Xingchun Tang, Pan Luo, Meng-Xiang Sun
{"title":"Reprogramming of microspore fate via BBM-BAR1 for highly efficient in vivo haploid induction","authors":"Ce Shi, Zifu Zhao, Yicheng Zhong, Ying Qiao, Lai Zhang, Fan Yang, Siyuan Li, Lulu Li, Lanjie Huang, Xingchun Tang, Pan Luo, Meng-Xiang Sun","doi":"10.1016/j.cell.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.014","url":null,"abstract":"Haploid induction (HI) through stress-treated microspore culture has gained significant attention for over half a century, yet the molecular mechanism underlying microspore fate transition for androgenesis remains poorly understood. Here, we demonstrate that microspore-specific expression of <em>BABY BOOM</em> (<em>BBM</em>) is sufficient to induce microspore cell fate transition and <em>in vivo</em> androgenesis in both tobacco and rice, effectively bypassing the requirement for stress treatment. We further identify <em>BBM-activated Androgenesis Regulator 1</em> (<em>BAR1</em>) as a novel downstream effector of BBM that promotes microspore reprogramming. Remarkably, both <em>BBM</em> and <em>BAR1</em> can replace the role of stress treatment in reprogramming microspore development and triggering androgenesis. This study reveals a conserved regulatory module governing androgenesis, providing a transformative approach to overcome long-standing limitations and enable highly efficient <em>in vivo</em> HI across diverse crops.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"61 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930869","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 de novo-originated gene drives rose scent diversification","authors":"Yajun Li, Runhui Li, Junzhong Shang, Kaige Zhao, Yaqi Sui, Zhenhua Liu, Huijun Yan, Manzhu Bao, Mei Liang, Qiao Zhao, Yao-Wu Yuan, Guogui Ning","doi":"10.1016/j.cell.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.011","url":null,"abstract":"How evolution builds genes, how these genes attain enhanced expression, and how they integrate into existing regulatory networks to drive phenotypic diversification are all fascinating questions. Here, we generated chromosome-level genome assemblies for two <em>Rosa banksiae</em> subspecies and re-sequenced an additional 40 rose accessions. Genomic analysis of more than 100 <em>Rosa</em> accessions revealed multiple evolutionary steps leading to the <em>de novo</em> origination of a taxon-restricted gene, <em>SCREP</em>, specific to the rose lineage. Extensive transcriptomic, metabolomic, and functional analyses demonstrated that the recruitment of a Miniature Inverted-repeat Transposable Element (MITE) transposon into the gene promoter led to elevated expression, that the gene <em>SCREP</em> orchestrates eugenol biosynthesis, and that the evolutionary dynamics of <em>SCREP</em> account for variation in rose scent among different species and cultivars. Our results provide insights into the mechanism of <em>de novo</em> gene origination, the role of transposable elements in gene expression, and the evolutionary consequences of taxon-restricted genes in phenotypic diversification.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"31 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928560","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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