IF 64.5 1区生物学

Cell Pub Date : 2026-09-22 DOI: 10.1016/j.cell.2026.08.043

H. Beryl Rappaport,Natalie A. Petek-Seoane,Tomáš Tyml,Jessica K. Niblo,Felix Mikus,Naomi E. Gilbert,Kurt LaButti,Godwin Ani,Ethan MacVicar,Rachel M. Shepherd,Ignacio de la Higuera,Samuel J. Lord,Gautam Dey,Gordon V. Wolfe,Omaya Dudin,Laura A. Katz,Kenneth M. Stedman,Shahar Sukenik,Kristen Skruber,Frederik Schulz,R. Dyche Mullins,Angela M. Oliverio

{"title":"A geothermal amoeba sets a new upper temperature limit for eukaryotes","authors":"H. Beryl Rappaport,Natalie A. Petek-Seoane,Tomáš Tyml,Jessica K. Niblo,Felix Mikus,Naomi E. Gilbert,Kurt LaButti,Godwin Ani,Ethan MacVicar,Rachel M. Shepherd,Ignacio de la Higuera,Samuel J. Lord,Gautam Dey,Gordon V. Wolfe,Omaya Dudin,Laura A. Katz,Kenneth M. Stedman,Shahar Sukenik,Kristen Skruber,Frederik Schulz,R. Dyche Mullins,Angela M. Oliverio","doi":"10.1016/j.cell.2026.08.043","DOIUrl":"https://doi.org/10.1016/j.cell.2026.08.043","url":null,"abstract":"The study of temperature limits has transformed our understanding of life’s boundaries but has focused on bacteria and archaea. For decades after their discovery, no eukaryote was shown to replicate above 60°C. We isolated a geothermal amoeba, Incendiamoeba cascadensis, that divides at 63°C and is motile up to 64°C. We identified an enrichment of genes related to proteostasis and environmental sensing relative to mesophilic amoebae. Comparative RNA sequencing of I. cascadensis revealed upregulation of pathways related to proteostasis, DNA repair, and membrane trafficking at high temperatures. Predicted proteins of I. cascadensis have distinct biophysical properties, including enrichment of positively charged surface residues similar to bacterial and archaeal hyperthermophiles, which suggests a convergent mechanism for protein stability under temperature stress. Together, our findings expand our understanding of where and how life can persist.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"33 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013595","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}

引用次数: 0

mRNA-encoding CD19-targeting T cell engager for refractory immune thrombocytopenia mrna编码cd19靶向T细胞接合物治疗难治性免疫性血小板减少症

IF 64.5 1区生物学

Cell Pub Date : 2026-09-18 DOI: 10.1016/j.cell.2026.08.039

Mengyan Wang,Tingting Liu,Qihua Dai,Jialin Teng,Yaping Wu,Jinchao Jia,Jianfen Meng,Yuning Ma,Hui Shi,Xiaobing Cheng,Honglei Liu,Yutong Su,Junna Ye,Huihui Chi,Zhuochao Zhou,Yue Sun,Yan Wu,Jia Chen,Wei Yin,Peng Gao,Wenjie Song,Rui Lin,Bo Ying,Chengde Yang,Qiongyi Hu

{"title":"mRNA-encoding CD19-targeting T cell engager for refractory immune thrombocytopenia","authors":"Mengyan Wang,Tingting Liu,Qihua Dai,Jialin Teng,Yaping Wu,Jinchao Jia,Jianfen Meng,Yuning Ma,Hui Shi,Xiaobing Cheng,Honglei Liu,Yutong Su,Junna Ye,Huihui Chi,Zhuochao Zhou,Yue Sun,Yan Wu,Jia Chen,Wei Yin,Peng Gao,Wenjie Song,Rui Lin,Bo Ying,Chengde Yang,Qiongyi Hu","doi":"10.1016/j.cell.2026.08.039","DOIUrl":"https://doi.org/10.1016/j.cell.2026.08.039","url":null,"abstract":"While T cell engagers (TCEs) and chimeric antigen receptor (CAR)-T cell therapy show clinical promise for B cell depletion, challenges regarding safety, efficacy, and durability persist. ABO2203 is a lipid nanoparticle-formulated messenger RNA (mRNA) encoding a CD19-targeting TCE. In transgenic mice, ABO2203 induced complete B cell depletion with attenuated cytokine release compared with TCE protein. In a first-in-human study involving three patients with refractory secondary immune thrombocytopenia, ABO2203 achieved rapid and complete peripheral B cell depletion, with sustained depletion in bone marrow. Patients exhibited durable platelet recovery, improved serology, and reduced disease activity through 6 months of follow-up. ABO2203 was well tolerated, presenting only grade 1 and 2 adverse events without cytokine release syndrome. B cell reconstitution was observed with predominant transitional and naive B cells. These findings establish mRNA-encoded TCEs as a potent and safer therapeutic modality for B cell-mediated autoimmune diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"197 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993805","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}

引用次数: 0

Oligodendrocytes in central nervous system health and disease 少突胶质细胞在中枢神经系统健康与疾病中的作用

IF 64.5 1区生物学

Cell Pub Date : 2026-09-18 DOI: 10.1016/j.cell.2026.08.003

Lucy J. Ryan,Veronique E. Miron

引用次数: 0

Chloroplasts balance energy production and stress resilience via a cold-induced signaling pathway 叶绿体通过冷诱导的信号通路平衡能量生产和应激恢复能力

IF 64.5 1区生物学

Cell Pub Date : 2026-09-18 DOI: 10.1016/j.cell.2026.08.041

Sujuan Duan,Yajun Zeng,Shuang Lin,Meihui Shi,Xiyan Chen,Pengxiang Zhang,Liu Hong,Jiayi Pan,Zhirong Chen,Jinfa Wang,Haiyang Wang,Hong-Bin Wang,Hong-Lei Jin

{"title":"Chloroplasts balance energy production and stress resilience via a cold-induced signaling pathway","authors":"Sujuan Duan,Yajun Zeng,Shuang Lin,Meihui Shi,Xiyan Chen,Pengxiang Zhang,Liu Hong,Jiayi Pan,Zhirong Chen,Jinfa Wang,Haiyang Wang,Hong-Bin Wang,Hong-Lei Jin","doi":"10.1016/j.cell.2026.08.041","DOIUrl":"https://doi.org/10.1016/j.cell.2026.08.041","url":null,"abstract":"Chloroplasts are plant-specific organelles for photosynthesis and play crucial roles in stress response. However, how chloroplasts respond to cold stress remains unclear. Here, we identify an rapidly accelerated fifibrosarcoma (RAF)-like bi-kinase module, RAF3/6, as key mediators in chloroplast cold-stress responses. RAF3/6 separately localize to the cytoplasm and plasma membrane under growth conditions. Upon cold stress, RAF3/6 translocate into chloroplasts mediated by the chaperone HSP70-1, where they phosphorylate the PSII components D1 and LHCB1, promoting their redistribution across thylakoid membranes and subsequent degradation, thereby suppressing photosynthetic activity. Concurrently, RAF3/6 phosphorylate the chloroplast-to-nucleus shuttling protein WHY1, promoting its nuclear accumulation and cold-defense gene activation. Notably, the natural variation of RAF6 contains a latitude-correlated SNP that affects its chloroplast import, suggesting an evolutionary cold adaptation. Together, these findings reveal a cold-induced outside-in signaling pathway that links cytoplasmic cold perception to chloroplast remodeling and nuclear defense, establishing a conceptual framework that balances energy production with stress resilience.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"52 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993822","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}

引用次数: 0

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository scBaseCount：一个AI代理策划的、标准化的、自动更新的单单元数据存储库

IF 64.5 1区生物学

Cell Pub Date : 2026-09-17 DOI: 10.1016/j.cell.2026.08.025

Nicholas D. Youngblut,Christopher Carpenter,Arshia Nayebnazar,Abhinav Adduri,Rohan Shah,Chiara Ricci-Tam,Jaanak Prashar,Rajesh Ilango,Noam Teyssier,Silvana Konermann,Patrick D. Hsu,Alexander Dobin,Dave P. Burke,Hani Goodarzi,Yusuf H. Roohani

{"title":"scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository","authors":"Nicholas D. Youngblut,Christopher Carpenter,Arshia Nayebnazar,Abhinav Adduri,Rohan Shah,Chiara Ricci-Tam,Jaanak Prashar,Rajesh Ilango,Noam Teyssier,Silvana Konermann,Patrick D. Hsu,Alexander Dobin,Dave P. Burke,Hani Goodarzi,Yusuf H. Roohani","doi":"10.1016/j.cell.2026.08.025","DOIUrl":"https://doi.org/10.1016/j.cell.2026.08.025","url":null,"abstract":"Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980633","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}

引用次数: 0

Changing minds: How AI is transforming the life sciences 改变思想：人工智能如何改变生命科学

IF 64.5 1区生物学

Cell Pub Date : 2026-09-17 DOI: 10.1016/j.cell.2026.08.019

Daphne Koller,Peilong Lu,Laura Cantini,Yuri Pritykin,Jean Yee Hwa Yang,Kanaka Rajan,Martin Steinegger,Mihaela van der Schaar

引用次数: 0

Dynamic dimer-of-dimers architecture defines Mg²⁺ transport in human CNNM4. 动态二聚体结构定义了Mg2+在人类CNNM4中的传输。

IF 45.1 1区生物学

Cell Pub Date : 2026-09-17 Epub Date: 2026-07-24 DOI: 10.1016/j.cell.2026.06.039

Zhiyong Bai, X Edward Zhou, Wei Lü, Juan Du

{"title":"Dynamic dimer-of-dimers architecture defines Mg2+ transport in human CNNM4.","authors":"Zhiyong Bai, X Edward Zhou, Wei Lü, Juan Du","doi":"10.1016/j.cell.2026.06.039","DOIUrl":"10.1016/j.cell.2026.06.039","url":null,"abstract":"Mg2+ is essential for all living organisms, yet its transport across mammalian membranes remains poorly understood. Here, we present cryoelectron microscopy (cryo-EM) structures of a full-length mammalian Mg2+ transporter on the plasma membrane, human CNNM4, in outward-facing and occluded states, revealing an unexpected tetrameric assembly organized as a dimer of asymmetric dimers-distinct from the symmetric dimers in prokaryotic homologs and long assumed for eukaryotic CNNMs. We show that Mg2+/ATP binding stabilizes the dynamic intracellular domains and promotes tetramerization, while an acidic patch binds additional Mg2+, potentially acting as a sensor to couple cytoplasmic Mg2+ levels to transport activity. Within the transmembrane domain, a key glutamate flips upon Na+ binding and destabilizes the Mg2+-binding site in the outward-facing state, thereby promoting Mg2+/Na+ exchange. Together, these findings establish a mechanistic framework for CNNM transport and regulation that diverges from prokaryotic models and links CNNM function to human physiology and disease.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"6097-6110.e4"},"PeriodicalIF":45.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583766","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}

引用次数: 0

A world model of the virtual cell 虚拟细胞的世界模型

IF 64.5 1区生物学

Cell Pub Date : 2026-09-17 DOI: 10.1016/j.cell.2026.08.042

Eric P. Xing,Le Song

{"title":"A world model of the virtual cell","authors":"Eric P. Xing,Le Song","doi":"10.1016/j.cell.2026.08.042","DOIUrl":"https://doi.org/10.1016/j.cell.2026.08.042","url":null,"abstract":"The prospect of an AI-driven digital organism (AIDO), such as a virtual cell, has recently captured growing excitement and imagination across the AI and biology communities. We envision a virtual cell as a multi-modal, multi-scale, dynamic, and stateful computational system capable of simulating the activity and behavior of a living cell. Such a system could shift cell biology from trial-and-error experimentation with cell-culture models in the wet lab toward systematic simulation of combinatorial interventions in a digital laboratory. In this paper, we propose the world model as an operational framework for realizing this vision—an emerging AI paradigm that supports action-conditioned simulation, counterfactual reasoning and long-horizon planning in complex dynamic environments. In this formulation, a virtual cell world model (VCWM) represents a persistent cellular state and simulates its evolution under genetic, chemical, environmental, and other biological interventions. In contrast to predictive foundation models optimized for specific tasks or endpoints, a VCWM seeks to model the underlying cellular system, allowing interventions to propagate through an evolving state and generate coherent molecular, structural, interactional, and morphological outcomes over time. We outline an architecture, a data framework, training strategy, and evaluation principles for realizing this vision and discuss how existing biological foundation models can serve as its building blocks. We envisage that VCWMs could transform biological discovery from exhaustive experimental search toward structured navigation of learned cellular worlds, enabling counterfactual exploration, rational intervention design, and ultimately more predictive, designable, and programmable cell biology.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"143 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980635","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}

引用次数: 0

Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer. 空间生物学揭示了免疫抑制非黑色素瘤皮肤癌中巨噬细胞状态的改变。

IF 45.1 1区生物学

Cell Pub Date : 2026-09-17 Epub Date: 2026-08-05 DOI: 10.1016/j.cell.2026.07.031

Shorook Naara, Veena Kochat, Xiayu Rao, Emre Arslan, Robert Saddawi-Konefka, Suresh Satpati, Jennifer Garbarino, Jennifer L Anderson, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Travis D Kerr, Shamima Akhter, Sophie Li, R'ay Fodor, Shlomo A Koyfman, Dan Yaniv, Tongxin Xie, Mica Glaun, Michael Bobian, William Israel Padron, Colin Ng, Preethi H Gunaratne, Shiyanth Thevasagayampillai, Michael R Migden, Hussein A Abbas, Patrick K Reville, Kenneth Y Tsai, Daniel J McGrail, Jing Wang, Jeffrey N Myers, Neil D Gross, Kunal Rai, Moran Amit

{"title":"Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer.","authors":"Shorook Naara, Veena Kochat, Xiayu Rao, Emre Arslan, Robert Saddawi-Konefka, Suresh Satpati, Jennifer Garbarino, Jennifer L Anderson, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Travis D Kerr, Shamima Akhter, Sophie Li, R'ay Fodor, Shlomo A Koyfman, Dan Yaniv, Tongxin Xie, Mica Glaun, Michael Bobian, William Israel Padron, Colin Ng, Preethi H Gunaratne, Shiyanth Thevasagayampillai, Michael R Migden, Hussein A Abbas, Patrick K Reville, Kenneth Y Tsai, Daniel J McGrail, Jing Wang, Jeffrey N Myers, Neil D Gross, Kunal Rai, Moran Amit","doi":"10.1016/j.cell.2026.07.031","DOIUrl":"10.1016/j.cell.2026.07.031","url":null,"abstract":"Immunosuppressed patients with non-melanoma skin cancer experience worse clinical outcomes, yet the tumor immune microenvironment associated with systemic immunosuppression remains incompletely defined. Using integrated single-cell, spatial transcriptomic, multiplex immunofluorescence, and spatial epigenomic profiling across immunocompetent and immunosuppressed tumors, we found that overall immune-cell composition was largely preserved despite differences in immune-cell distribution, spatial organization, and T cell clonality. Immunosuppressed tumors demonstrated reduced intratumoral macrophage densities, decreased T cell clonal diversity, altered antigen-presenting cell and T cell spatial interactions, and distinct fibroblast- and macrophage-associated spatial niches. Multi-cohort validation across complementary spatial and single-cell platforms identified consistent alterations in innate-adaptive immune organization in immunosuppressed tumors. Together, these findings define spatial and functional remodeling of the tumor immune microenvironment under systemic immunosuppression and provide a framework for future therapeutic investigation in high-risk patients.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"6170-6188.e9"},"PeriodicalIF":45.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677307","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}

引用次数: 0

Toward autonomous science with agentic artificial intelligence 用人工智能走向自主科学

IF 64.5 1区生物学

Cell Pub Date : 2026-09-17 DOI: 10.1016/j.cell.2026.08.052

Lucie Y. Guo,Darren S.J. Ting,Xinyi Su,Alex Aliper,Alex Zhavoronkov,Daniel S.W. Ting

引用次数: 0

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