CellPub Date : 2025-09-23DOI: 10.1016/j.cell.2025.09.015
Maria Ciofani, Aviv Madar, Carolina Galan, MacLean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, Wendy Huang, Christopher N. Parkurst, Michael Muratet, Kim M. Newberry, Sarah Meadows, Alex Greenfield, Yi Yang, Preti Jain, Francis K. Kirigin, Carmen Birchmeier, Erwin F. Wagner, Kenneth M. Murphy, Richard M. Myers, Dan R. Littman
{"title":"A Validated Regulatory Network for Th17 Cell Specification","authors":"Maria Ciofani, Aviv Madar, Carolina Galan, MacLean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, Wendy Huang, Christopher N. Parkurst, Michael Muratet, Kim M. Newberry, Sarah Meadows, Alex Greenfield, Yi Yang, Preti Jain, Francis K. Kirigin, Carmen Birchmeier, Erwin F. Wagner, Kenneth M. Murphy, Richard M. Myers, Dan R. Littman","doi":"10.1016/j.cell.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.015","url":null,"abstract":"(Cell <em>151</em>, 289–303; October 12, 2012)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"84 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127334","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 : 2025-09-22DOI: 10.1016/j.cell.2025.08.034
Maria Akopyan, Matthew Genchev, Ellie E. Armstrong, Jazlyn A. Mooney
{"title":"Reference genome choice compromises population genetic analyses","authors":"Maria Akopyan, Matthew Genchev, Ellie E. Armstrong, Jazlyn A. Mooney","doi":"10.1016/j.cell.2025.08.034","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.034","url":null,"abstract":"Characterizing genetic variation in natural populations is vital to evolutionary biology; however, many non-model species lack genomic resources. Here, we demonstrate that reference bias significantly affects population genomic analyses by mapping whole-genome sequence data from gray foxes (<em>Urocyon cinereoargenteus</em>) to a conspecific reference and two heterospecific canid genomes (dog and Arctic fox). Mapping to the conspecific genome improved read pairing by ∼5% and detected 26%–32% more SNPs and 33%–35% more singletons. Nucleotide diversity estimates increased by over 30%, <em>F</em><sub>ST</sub> increased from 0.189 to 0.197, and effective population size estimates were 30%–60% higher with the conspecific reference. Recombination rates varied by up to 3-fold at chromosome ends with heterospecific references. Importantly, <em>F</em><sub>ST</sub> outlier detection differed markedly, with heterospecific genomes identifying twice as many unique outlier windows. These findings highlight the impact of reference genome choice and the importance of conspecific genomic resources for accurate evolutionary inference.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"24 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103772","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 : 2025-09-22DOI: 10.1016/j.cell.2025.08.035
Zizhu Tan, Chia-Heng Hsiung, Jiahui Feng, Yangye Zhang, Yihan Wan, Junlin Chen, Ke Sun, Peilong Lu, Jianyang Zang, Wenxing Yang, Ya Gao, Jiabin Yin, Tong Zhu, Yang Lu, Zijian Pan, Yilong Zou, Can Liao, Xiaosong Li, Yuxuan Ye, Yu Liu, Xin Zhang
{"title":"Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains","authors":"Zizhu Tan, Chia-Heng Hsiung, Jiahui Feng, Yangye Zhang, Yihan Wan, Junlin Chen, Ke Sun, Peilong Lu, Jianyang Zang, Wenxing Yang, Ya Gao, Jiabin Yin, Tong Zhu, Yang Lu, Zijian Pan, Yilong Zou, Can Liao, Xiaosong Li, Yuxuan Ye, Yu Liu, Xin Zhang","doi":"10.1016/j.cell.2025.08.035","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.035","url":null,"abstract":"Fluorescence microscopy has been widely applied in the life sciences. While intensity as a steady-state signal is widely used, the time-resolved (tr) signal using fluorescence lifetime remains underexplored. Herein, we present a family of time-resolved fluorescent proteins (tr-FPs) with rationally controlled lifetimes. Using a strategy that regulates lifetime without affecting the spectra of FPs, we have developed a series of tr-FPs that cover the visible spectrum and a wide range of lifetimes. The tr-FPs are employed in temporal-spectral resolved microscopy, allowing for the simultaneous imaging of 9 different proteins in live cells and the correlation of multiple activities to cell cycles. Furthermore, tr-FPs enable multiplexing super-resolution microscopy that concurrently visualizes 4 proteins using the lifetime signal and are demonstrated to quantify the stoichiometry of cellular proteins. Our work introduces the concept and development of tr-FPs as a transformative toolset, presenting opportunities to integrate system complexity and quantitative accuracy into biological research.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"317 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103773","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 : 2025-09-18DOI: 10.1016/j.cell.2025.08.030
James H. Leebens-Mack
{"title":"Hybrid genome spawns tuber development and potato diversity","authors":"James H. Leebens-Mack","doi":"10.1016/j.cell.2025.08.030","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.030","url":null,"abstract":"In this issue of <em>Cell</em>, Huang and colleagues reveal how ancient hybridization between ancestors of tomato and a related wild species, <em>Solanum etuberosum,</em> enabled the origin of tuber formation and the diversification of potato species. Their genomic analyses highlight how interactions between genes derived from distinct progenitors can drive development of novel traits in hybrids.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078558","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 : 2025-09-18DOI: 10.1016/j.cell.2025.08.025
Hejia Henry Wang, Neeha Zaidi
{"title":"Multi-adjuvant personalized neoantigen vaccines: Fine-tuning anti-cancer T cells","authors":"Hejia Henry Wang, Neeha Zaidi","doi":"10.1016/j.cell.2025.08.025","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.025","url":null,"abstract":"Personalized cancer vaccines aim to broaden the anti-tumor T cell repertoire by targeting neoantigens unique to each patient’s tumor, but immunogenicity has been inconsistent. In this issue of <em>Cell</em>, Blass, Keskin, Tu et al. evaluate NeoVax<sup>MI</sup>, a multi-adjuvant personalized synthetic long-peptide vaccine administered with nivolumab in patients with melanoma. NeoVax<sup>MI</sup> elicited stronger CD4<sup>+</sup> and CD8<sup>+</sup> responses than earlier iterations, and vaccine-induced T cells trafficked to regressing metastatic lesions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078362","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 : 2025-09-17DOI: 10.1016/j.cell.2025.08.029
Khristian E. Bauer-Rowe, Benjamin Pham, Michelle Griffin, Norah E. Liang, Alexia Kim, John M. Lu, Michael Januszyk, Jason L. Guo, Stefania De Santis, Yue Xing, Aleksandr Prystupa, Ikjot Sidhu, Elijah J. Suh, Deshka S. Foster, Maria Korah, Alka Goyal, Derrick C. Wan, Jeffrey A. Norton, Daniel Delitto, Theresa T. Pizarro, Michael T. Longaker
{"title":"Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures","authors":"Khristian E. Bauer-Rowe, Benjamin Pham, Michelle Griffin, Norah E. Liang, Alexia Kim, John M. Lu, Michael Januszyk, Jason L. Guo, Stefania De Santis, Yue Xing, Aleksandr Prystupa, Ikjot Sidhu, Elijah J. Suh, Deshka S. Foster, Maria Korah, Alka Goyal, Derrick C. Wan, Jeffrey A. Norton, Daniel Delitto, Theresa T. Pizarro, Michael T. Longaker","doi":"10.1016/j.cell.2025.08.029","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.029","url":null,"abstract":"A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to form a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue around diseased bowel, of which the role in CD stricture progression is unclear. By constructing a human single-cell CD fibroblast atlas, we identified CF-derived, CTHRC1+ fibroblasts enriched for Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signatures and localized to a fibrotic CF-bowel wall interface within the stricture. We further showed that analogous Cthrc1+ mouse fibroblasts derive from mesenteric adipose tissue stromal cells, infiltrate fibrotic bowel, and deposit extracellular matrix in a YAP/TAZ-dependent manner in a mouse model of intestinal fibrosis. Our findings identify CF as a key source of pro-fibrotic fibroblasts and raise the possibility of improving future clinical management of stricture progression by targeting not only the bowel but also CF.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"109 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072045","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":"Distinct circuit motifs evaluate opposing innate values of odors","authors":"Makoto Someya, Ka-Yuet Liu, Kazumi Ohta, Hokto Kazama","doi":"10.1016/j.cell.2025.08.032","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.032","url":null,"abstract":"Evaluating the innate value of objects is critical for expressing adaptive behaviors. However, where and how this computation takes place in the brain remain elusive. By recording from virtually every neuron in <em>Drosophila</em> higher olfactory areas, we show that the lateral horn is a site of innate odor value computation, where distinct neurons represent opposing innate values. A connectome-based spiking network model recapitulating the neural activity indicates that representations of aversive odors emerge through specific convergence of feedforward excitation, whereas those of attractive odors emerge through additional local inhibition. This inhibition is broad yet balanced with excitation and implements gain control and thresholding to shape attractive odor tuning. Manipulation of local inhibition biased neuronal and behavioral odor responses according to the prediction of the model. Thus, odors at the opposite ends of the hedonic spectrum are processed in sub-circuits that are not only segregated but also distinct in connectivity motifs.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"88 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072047","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 : 2025-09-16DOI: 10.1016/j.cell.2025.08.031
Li Ping Tang, Li Ming Zhai, Jiming Li, Yue Gao, Qiu Li Ma, Rui Li, Qing Fei Liu, Wen Jie Zhang, Wang Jinsong Yao, Bangbang Mu, Chao Qin, Xin Tian, Rahul Shaw, Keke Xia, Jian Xu, Ying Hua Su, Xian Sheng Zhang
{"title":"Time-resolved reprogramming of single somatic cells into totipotent states during plant regeneration","authors":"Li Ping Tang, Li Ming Zhai, Jiming Li, Yue Gao, Qiu Li Ma, Rui Li, Qing Fei Liu, Wen Jie Zhang, Wang Jinsong Yao, Bangbang Mu, Chao Qin, Xin Tian, Rahul Shaw, Keke Xia, Jian Xu, Ying Hua Su, Xian Sheng Zhang","doi":"10.1016/j.cell.2025.08.031","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.031","url":null,"abstract":"Totipotency enables single cells to regenerate an organism, yet how differentiated somatic cells reacquire this potential remains unclear. Here, we show that <em>LEAFY COTYLEDON2</em> (LEC2) reprograms <em>SPEECHLESS</em> (<em>SPCH</em>)-expressing meristemoid mother cells (MMCs) away from stomatal-lineage progression, driving their conversion into totipotent somatic embryo founder cells (SEFCs) in Arabidopsis cotyledons. Using time-course live imaging, single-nucleus RNA sequencing (snRNA-seq), and spatial laser capture microdissection combined with RNA sequencing (LCM-RNA-seq), we uncover a lineage bifurcation point where MMC derivatives either commit to guard cells or transition into a guard mother cell (GMC)-auxin intermediate, an auxin-enriched state that enables transcriptional reprogramming and embryonic gene activation. LEC2 and SPCH cooperatively activate <em>TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1</em> (<em>TAA1</em>) and <em>YUCCA4</em> (<em>YUC4</em>), establishing a local auxin biosynthesis circuit essential for SEFC specification. Genetic and promoter analyses confirm MMCs as the origin of somatic embryos, with <em>TAA1</em>/<em>YUC</em>-mediated auxin production indispensable for totipotency and embryogenesis. These findings define an auxin-driven, transcriptionally regulated trajectory linking stomatal progenitors to somatic embryogenesis, revealing a direct route that advances mechanistic understanding of plant regenerative plasticity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"17 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068047","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 : 2025-09-16DOI: 10.1016/j.cell.2025.08.028
Samson Glaser, Maxim I. Molodtsov, John F.X. Diffley, Frank Uhlmann
{"title":"Replisome passage through the cohesin ring","authors":"Samson Glaser, Maxim I. Molodtsov, John F.X. Diffley, Frank Uhlmann","doi":"10.1016/j.cell.2025.08.028","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.028","url":null,"abstract":"Following eukaryotic genome replication, the ring-shaped cohesin complex embraces the two newly synthesized sister chromatids, enabling their faithful segregation during cell divisions. Replisome passage through cohesin rings has been envisioned as a fail-safe mechanism that ensures co-entrapment of replication products—whether replisomes can indeed pass through cohesin rings remains unknown. Here, we use biochemical reconstitution and single-molecule fluorescence microscopy to directly visualize replisome-cohesin encounters. We find that the translocating eukaryotic replicative Cdc45-Mcm2-7-GINS (CMG) helicase, unlike other obstacles of similar size, readily passes through cohesin rings. Fully reconstituted replisomes also pass cohesin rings to leave both replication products trapped inside. Replisome passage is primarily aided by DNA polymerases α and ε, a finding that necessitates re-evaluation of canonical cohesion establishment factor roles. Our findings demonstrate the existence of a simple mechanism that links genome replication with chromosome segregation: replisome passage through cohesin rings.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"36 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068046","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 : 2025-09-15DOI: 10.1016/j.cell.2025.08.027
Samuel J. Vidal, Ninaad Lasrado, Lisa H. Tostanoski, Jayeshbhai Chaudhari, Esther R. Mbiwan, Ganad D. Neka, Ellis A. Strutton, Alejandro A. Espinosa Perez, Daniel Sellers, Julia Barrett, Michelle Lifton, Shoko Wakabayashi, Behnaz Eshaghi, Erica N. Borducchi, Malika Aid, Wenjun Li, Thomas J. Scriba, Ana Jaklenec, Robert Langer, Dan H. Barouch
{"title":"Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines","authors":"Samuel J. Vidal, Ninaad Lasrado, Lisa H. Tostanoski, Jayeshbhai Chaudhari, Esther R. Mbiwan, Ganad D. Neka, Ellis A. Strutton, Alejandro A. Espinosa Perez, Daniel Sellers, Julia Barrett, Michelle Lifton, Shoko Wakabayashi, Behnaz Eshaghi, Erica N. Borducchi, Malika Aid, Wenjun Li, Thomas J. Scriba, Ana Jaklenec, Robert Langer, Dan H. Barouch","doi":"10.1016/j.cell.2025.08.027","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.027","url":null,"abstract":"Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, and Bacillus Calmette-Guérin (BCG) remains the only clinically approved vaccine. An enduring challenge in TB vaccine development is systematic antigen selection from a large repertoire of potential candidates. We performed an efficacy screen in mice of antigens that are targets of CD4 T cells in humans. We found striking heterogeneity in protective efficacy, and most of the top protective antigens are not currently in clinical development. We observed immunologic cross-reactivity among phylogenetically clustered antigens, reflecting common CD4 epitopes. We developed a trivalent mRNA vaccine consisting of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which augmented and exceeded BCG protection in multiple mouse models. Finally, we observed cellular immune responses to these antigens in 84% of humans exposed to <em>M. tuberculosis</em>. These data advance our understanding of TB vaccine immunology and define a vaccine concept for clinical development.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"51 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059698","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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