IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.005

Lingfeng Gou, Yanzhi Wang, Le Gao, Sang Liu, Mingli Wang, Qinwen Chai, Jiao Fang, Lijie Zhan, Xiaowen Shen, Tao Jiang, Wenqiang Ren, Miao Ren, Xueyan Jia, Chi Xiao, Anan Li, Xiangning Li, Qingming Luo, Gouki Okazawa, Tianming Yang, Zhen Liu, Jun Yan

{"title":"Single-neuron projectomes of macaque prefrontal cortex reveal refined axon targeting and arborization","authors":"Lingfeng Gou, Yanzhi Wang, Le Gao, Sang Liu, Mingli Wang, Qinwen Chai, Jiao Fang, Lijie Zhan, Xiaowen Shen, Tao Jiang, Wenqiang Ren, Miao Ren, Xueyan Jia, Chi Xiao, Anan Li, Xiangning Li, Qingming Luo, Gouki Okazawa, Tianming Yang, Zhen Liu, Jun Yan","doi":"10.1016/j.cell.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.005","url":null,"abstract":"Cortical expansion endows advanced cognitive functions in primates, and whole-brain single-neuron projection analysis helps to elucidate underlying neural circuit mechanisms. Here, we reconstructed 2,231 single-neuron projectomes for the macaque prefrontal cortex (PFC) and identified 32 projectome-based subtypes of intra-telencephalic, pyramidal-tract, and cortico-thalamic neurons. Each subtype exhibited distinct topography in their soma distribution within the PFC, a characteristic pattern of axon targeting, and subregion-specific patchy terminal arborization in the targeted area, with putative functions annotated. Furthermore, we identified a subdomain connectivity network and extensive local axons within the PFC. Compared with those in mice, macaque PFC projectomes exhibited a similar topographic gradient of terminal arborization at the targeted regions but much higher target specificity, fewer collaterals, and smaller brain size-normalized arbors. Thus, whole-brain single-axon macaque projectomes revealed highly refined axon targeting and arborization, providing key insights into the structural basis for complex brain functions in primates.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"710 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594759","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

The generative era of medical AI 医疗人工智能的生成时代

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.05.018

L. John Fahrner, Emma Chen, Eric Topol, Pranav Rajpurkar

引用次数: 0

Identification and application of cell-type-specific enhancers for the macaque brain 猕猴脑细胞类型特异性增强子的鉴定与应用

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.040

Ling Li, Yiming Huang, Dengyu Lu, Jiqiang Fu, Luyan Wu, Zheyuan Chen, Haiou Liao, Jiaqi Zhang, Li Li, Tianyue Gu, Fang He, Hean Liu, Xiangqing Leng, Jing Tang, Jiaqi Yan, Cirong Liu, Chao Li, Huapin Huang, Lina Wang, Longqi Liu, Zhen Liu

{"title":"Identification and application of cell-type-specific enhancers for the macaque brain","authors":"Ling Li, Yiming Huang, Dengyu Lu, Jiqiang Fu, Luyan Wu, Zheyuan Chen, Haiou Liao, Jiaqi Zhang, Li Li, Tianyue Gu, Fang He, Hean Liu, Xiangqing Leng, Jing Tang, Jiaqi Yan, Cirong Liu, Chao Li, Huapin Huang, Lina Wang, Longqi Liu, Zhen Liu","doi":"10.1016/j.cell.2025.06.040","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.040","url":null,"abstract":"Genetic targeting methods for monitoring and manipulating neuronal activity are not widely used for studying the primate brain, largely owing to the lack of a cell-type-specific targeting method. Using single-cell RNA and ATAC sequencing of macaque brains combined with in vivo screening, we identified a large set of enhancers capable of driving targeted gene expression in specific cell types. AAV vectors driven by these enhancers successfully targeted layer-specific glutamatergic neurons, GABAergic interneuron subtypes, astrocytes, and oligodendrocytes with high specificity. Cross-species comparison revealed that some macaque enhancers are conserved and functional across species, but enhancers with layer-specific targeting in macaques did not label neurons in mice, highlighting evolutionary differences in cortical CREs. Targeting precision was further improved using a FLPo-dependent intersectional approach with two enhancers. These enhancer-AAVs were validated by monitoring and manipulating activity in macaque visual cortex, providing valuable tools to dissect primate neural circuit functions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"279 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602979","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

Targeting serotonin transporter boosts tumor-fighting T cells 靶向血清素转运体促进抗肿瘤T细胞

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.012

Michael D. Gershon

引用次数: 0

Mesoscopic mapping of the brain: From rodents to primates 大脑的介观图：从啮齿动物到灵长类动物

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.013

Yan-Gang Sun, Qingming Luo, Mu-Ming Poo

引用次数: 0

Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo 联合抗逆转录病毒治疗和MCL-1抑制可减轻体内HTLV-1感染

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.023

James P. Cooney, Ashley Hirons, Natasha Jansz, Cody C. Allison, Peter Hickey, Charis E. Teh, Tania Tan, Laura F. Dagley, Jumana Yousef, David Yurick, Georges Khoury, Simon P. Preston, Philip Arandjelovic, Kathryn C. Davidson, Lewis J. Williams, Stefanie M. Bader, Le Wang, Reet Bhandari, Liana Mackiewicz, Merle Dayton, Marc Pellegrini

{"title":"Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo","authors":"James P. Cooney, Ashley Hirons, Natasha Jansz, Cody C. Allison, Peter Hickey, Charis E. Teh, Tania Tan, Laura F. Dagley, Jumana Yousef, David Yurick, Georges Khoury, Simon P. Preston, Philip Arandjelovic, Kathryn C. Davidson, Lewis J. Williams, Stefanie M. Bader, Le Wang, Reet Bhandari, Liana Mackiewicz, Merle Dayton, Marc Pellegrini","doi":"10.1016/j.cell.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.023","url":null,"abstract":"This study investigated preventative and therapeutic agents against human T cell lymphotropic virus type-1 subtype-C (HTLV-1c) infection. We established and characterized a humanized mouse model of HTLV-1c infection and identified that HTLV-1c disease appears slightly more aggressive than the prevalent HTLV-1 subtype-A (HTLV-1a), which may underpin increased risk for infection-associated pulmonary complications in HTLV-1c. Combination antiretroviral therapy with tenofovir and dolutegravir at clinically relevant doses significantly reduced HTLV-1c transmission and disease progression in vivo. Single-cell RNA sequencing (scRNA-seq) and intracellular flow cytometry identified that HTLV-1c infection leads to dysregulated intrinsic apoptosis in infected cells in vivo. Pharmacological inhibition using BH3 mimetic compounds against MCL-1, but not BCL-2, BCL-XL, or BCL-w, killed HTLV-1c-infected cells in vitro and in vivo and significantly delayed disease progression when combined with tenofovir and dolutegravir in mice. Our data suggest that combination antiretroviral therapy with MCL-1 antagonism may represent an effective, clinically relevant, and potentially curative strategy against HTLV-1c.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"23 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594799","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

Burst firing in Alzheimer’s disease: A shift beyond amyloid? 阿尔茨海默病的突发放电：超越淀粉样蛋白的转变？

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.016

Luísa V. Lopes, Paula A. Pousinha

引用次数: 0

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution 亚细胞分辨率下全鼠周围神经的高速制图

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.011

Mei-Yu Shi, Yuchen Yao, Miao Wang, Qi Yang, Lufeng Ding, Rui Li, Yuanyuan Li, Haimeng Huang, Chao-Yu Yang, Zhao Zhou, Zhenxiang Zhu, Pengjie Wen, Fangling Dai, Xiaohui Zeng, Ke-Ming Zhang, Yuhong Guo, Zi-An Sun, Huanhuan Xia, Zhenhua Ren, Yusuf Ozgur Cakmak, Guo-Qiang Bi

{"title":"High-speed mapping of whole-mouse peripheral nerves at subcellular resolution","authors":"Mei-Yu Shi, Yuchen Yao, Miao Wang, Qi Yang, Lufeng Ding, Rui Li, Yuanyuan Li, Haimeng Huang, Chao-Yu Yang, Zhao Zhou, Zhenxiang Zhu, Pengjie Wen, Fangling Dai, Xiaohui Zeng, Ke-Ming Zhang, Yuhong Guo, Zi-An Sun, Huanhuan Xia, Zhenhua Ren, Yusuf Ozgur Cakmak, Guo-Qiang Bi","doi":"10.1016/j.cell.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.011","url":null,"abstract":"In contrast to the rapid advancements in mesoscale connectomic mapping of the mammalian brain, similar mapping of the peripheral nervous system has remained challenging due to the body size and complexity. Here, we present a high-speed blockface volumetric imaging system with an optimized workflow of whole-body clearing, capable of imaging the entire adult mouse at micrometer resolution within 40 h. Three-dimensional reconstruction of individual spinal fibers in Thy1-EGFP mice reveals distinct morphological features of sensory and motor projections along the ventral and dorsal rami. Immunostaining facilitates body-wide mapping of sympathetic nerves and their branches, highlighting their perivascular patterns in limb muscles, bones, and most visceral organs. Viral tracing elucidates the fine architecture of vagus nerves and individual vagal fibers, revealing unexpected projection routes to various organs. Our approach offers an effective means to achieve a holistic understanding of cellular-level interactions among different systems that underlie body physiology and disease.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594800","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

A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma 多佐剂个人新抗原疫苗在黑色素瘤中产生强效免疫

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.019

Eryn Blass, Derin B. Keskin, Chloe R. Tu, Cleo Forman, Allison Vanasse, Haley E. Sax, Bohoon Shim, Vipheaviny Chea, Nawoo Kim, Isabel Carulli, Jackson Southard, Haoxiang Lyu, Wesley Lu, Micah Rickles-Young, Alexander B. Afeyan, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Joanna Baginska, Patrick A. Ott

{"title":"A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma","authors":"Eryn Blass, Derin B. Keskin, Chloe R. Tu, Cleo Forman, Allison Vanasse, Haley E. Sax, Bohoon Shim, Vipheaviny Chea, Nawoo Kim, Isabel Carulli, Jackson Southard, Haoxiang Lyu, Wesley Lu, Micah Rickles-Young, Alexander B. Afeyan, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Joanna Baginska, Patrick A. Ott","doi":"10.1016/j.cell.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.019","url":null,"abstract":"Personalized neoantigen-targeting vaccines have demonstrated great promise; however, improved immunogenicity is still needed. Since antigen availability and effective T cell priming are critical for maximal immunogenicity, we tested a synthetic long peptide vaccine formulated with Montanide, poly-ICLC, and locally administered ipilimumab in addition to systemic nivolumab in 10 patients with melanoma. These personalized vaccines generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients and ex vivo CD8+ T cell responses in 6 of 9. Vaccination induced hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes that were distinct from those arising after PD-1 inhibition. By linking the vaccine neoantigen specificity of T cell clonotypes with single-cell phenotypes in tumors, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations show that multi-pronged immune adjuvanticity can boost T cell responses to neoantigen-targeting vaccines.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"697 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594755","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

A clinical road map for single-cell omics 单细胞组学的临床路线图

IF 64.5 1区生物学

Cell Pub Date : 2025-07-10 DOI: 10.1016/j.cell.2025.06.009

Michael A. Skinnider, Gregoire Courtine, Jocelyne Bloch, Jordan W. Squair

{"title":"A clinical road map for single-cell omics","authors":"Michael A. Skinnider, Gregoire Courtine, Jocelyne Bloch, Jordan W. Squair","doi":"10.1016/j.cell.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.cell.2025.06.009","url":null,"abstract":"In a matter of years, single-cell omics has matured from a pioneering technique employed by just a handful of specialized laboratories to become a ubiquitous feature of biological research and a key driver of scientific discovery. The widespread adoption and development of single-cell omic assays has sparked mounting enthusiasm that these technologies are poised to also enhance the precision of diagnosis, the monitoring of disease progression, and the personalization of therapeutic strategies. Despite initial forays into clinical settings, however, single-cell technologies are not yet routinely used to inform medical or surgical decision-making. Here, we identify and categorize key experimental, computational, and conceptual barriers that currently hinder the clinical deployment of single-cell omics. We focus on the potential for single-cell transcriptomics to guide clinical decision-making through the development of combinatorial biomarkers that simultaneously quantify multiple cell-type-specific pathophysiological processes. We articulate a framework to identify patient subpopulations that stand to benefit from such biomarkers, and we outline the experimental and computational requirements to derive reproducible and actionable clinical readouts from single-cell omics.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"11 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594801","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

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