IF 64.5 1区生物学

Cell Pub Date : 2026-04-21 DOI: 10.1016/j.cell.2026.03.040

August Yue Huang, Zinan Zhou, Maya Talukdar, Liz Enyenihi, Michael B. Miller, Brian Chhouk, Ila Rosen, Mengyue Zheng, Minye Zhou, Averill Yang, Edward Stronge, Madel Durens, Minh Nguyen, Jaejoon Choi, Boxun Zhao, Sattar Khoshkhoo, Junho Kim, Rebecca Andersen, Zheming An, Yuchen Cheng, Christopher A. Walsh

{"title":"Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states","authors":"August Yue Huang, Zinan Zhou, Maya Talukdar, Liz Enyenihi, Michael B. Miller, Brian Chhouk, Ila Rosen, Mengyue Zheng, Minye Zhou, Averill Yang, Edward Stronge, Madel Durens, Minh Nguyen, Jaejoon Choi, Boxun Zhao, Sattar Khoshkhoo, Junho Kim, Rebecca Andersen, Zheming An, Yuchen Cheng, Christopher A. Walsh","doi":"10.1016/j.cell.2026.03.040","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.040","url":null,"abstract":"Alzheimer’s disease (AD) is a neurodegenerative condition characterized by microglia-mediated neuroinflammation. Deep (>1,000×) panel sequencing of 311 brain samples revealed enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes in AD brains, especially in genes associated with clonal hematopoiesis (CH). These sSNVs were associated with clonal expansion and carried by both microglia-like brain macrophages (MLBMs) in multiple brain regions as well as paired blood, suggesting a likely hematopoietic origin. Single-nucleus RNA sequencing data from 62 additional AD and control brains revealed increased somatic copy number variants (sCNVs) associated with CH in AD MLBMs, whereas single-cell multi-omic analyses demonstrated that sSNV- and sCNV-carrying MLBMs exhibited inflammatory and proliferative transcriptional signatures characteristic of disease-associated microglia. These signatures were recapitulated in induced pluripotent stem cell-derived microglia-like cells with TET2, ASXL1, and DNMT3A variants. These findings suggest that clonal somatic driver variants in MLBMs are enriched in AD, potentially promoting neuroinflammation and neurodegeneration.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"10 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735934","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 evolution of high-order genome architecture revealed from 1,000 species. 1000个物种高阶基因组结构的进化。

IF 42.5 1区生物学

Cell Pub Date : 2026-04-21 DOI: 10.1016/j.cell.2026.03.042

Yizhuo Che, Stephen J Bush, Hui Lin, Mingxuan Li, Xiaofei Yang, Qi Xie, Yuchun Liu, Deyu Meng, Kai Ye

{"title":"The evolution of high-order genome architecture revealed from 1,000 species.","authors":"Yizhuo Che, Stephen J Bush, Hui Lin, Mingxuan Li, Xiaofei Yang, Qi Xie, Yuchun Liu, Deyu Meng, Kai Ye","doi":"10.1016/j.cell.2026.03.042","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.042","url":null,"abstract":"Spatial genome organization plays a crucial regulatory role, but its evolutionary development remains unclear. Leveraging Hi-C data from 1,025 species, we trace the evolutionary trajectories of genome organization through 2 higher-order architectures, \"global folding\" (spatial organization of the karyotype) and \"checkerboard\" (spatial organization of chromatin compartments). Earlier unicellular life forms mostly displayed random genome configurations. Throughout the evolution of plants, global folding became and remained the prominent architecture. However, animals progressively developed more pronounced checkerboard architectures; these are also apparent during early embryogenesis, which suggests that they act as a conserved mechanism of gene regulation. In contrast, plants exhibit comparatively weaker checkerboard patterns and instead preferentially organize co-regulated genes into linear genomic clusters. Both strategies of gene arrangement reinforce the biological principle that \"structure determines function\": divergent evolutionary paths converge on architectural solutions that reflect gene regulatory requirements over time.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763484","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 skin-hypothalamus axis couples heat stress and metabolic dysfunction 皮肤-下丘脑轴与热应激和代谢功能障碍有关

IF 64.5 1区生物学

Cell Pub Date : 2026-04-21 DOI: 10.1016/j.cell.2026.03.045

Hai-Yan Zhou, Xu Feng, Jie Wen, Yao Xiao, Li-Wen Wang, Lin-Yun Chen, Gen-Qing Xie, Jia-Jun Zhao, Yan Huang, Xiang-Hang Luo

{"title":"A skin-hypothalamus axis couples heat stress and metabolic dysfunction","authors":"Hai-Yan Zhou, Xu Feng, Jie Wen, Yao Xiao, Li-Wen Wang, Lin-Yun Chen, Gen-Qing Xie, Jia-Jun Zhao, Yan Huang, Xiang-Hang Luo","doi":"10.1016/j.cell.2026.03.045","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.045","url":null,"abstract":"With the ongoing rise in global temperatures, the prevalence of heat-stress-related chronic health disorders has increased. However, whether heat stress has an enduring impact on metabolic health remains unclear. Here, we report that mice exposed to heat stress were more susceptible to metabolic dysfunction upon subsequent exposure to an obesogenic diet. Upon heat stress, we found that elevated skin-derived kallikrein-related peptidase 14 (KLK14) imprinted hypothalamic LRRC7+ astrocytes. These astrocytes further suppressed neighboring paraventricular nucleus (PVN)OXT neuron activity via alkB homolog 1, histone H2A dioxygenase (ALKBH1)-mediated epigenetic modification of γ-aminobutyric acid (GABA) synthesis, thus driving visceral fat deposition in a sympathetic nervous-system-dependent manner. Heat stress exposure also increased susceptibility to metabolic dysfunction in human subjects, with vitamin A treatment limiting the production of KLK14 and ameliorating metabolic disturbances in humans and mice. Together, our findings reveal a skin-hypothalamus axis linking heat memory and metabolic dysfunction and highlight that global warming is exacerbating metabolic diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147732283","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

Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells 在人CD4+ T细胞中系统发现hiv宿主因子

IF 64.5 1区生物学

Cell Pub Date : 2026-04-20 DOI: 10.1016/j.cell.2026.03.046

Ujjwal Rathore, Eli Dugan, Hunter Thornton, Vigneshwari Easwar Kumar, Rama Dajani, Ryan C. Burdick, Janet M. Young, Zachary Steinhart, Reanna Lao, Krista A. Delviks-Frankenberry, Wooyoung Choi, William S. Henriques, Ignacia Echeverria, Emma Dann, Ishaan Dureja, Nandini Pathak, Maya M. Arce, Justin McKetney, Jennifer M. Umhoefer, Simrun Parulekar, Alexander Marson

{"title":"Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells","authors":"Ujjwal Rathore, Eli Dugan, Hunter Thornton, Vigneshwari Easwar Kumar, Rama Dajani, Ryan C. Burdick, Janet M. Young, Zachary Steinhart, Reanna Lao, Krista A. Delviks-Frankenberry, Wooyoung Choi, William S. Henriques, Ignacia Echeverria, Emma Dann, Ishaan Dureja, Nandini Pathak, Maya M. Arce, Justin McKetney, Jennifer M. Umhoefer, Simrun Parulekar, Alexander Marson","doi":"10.1016/j.cell.2026.03.046","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.046","url":null,"abstract":"Host factors that promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells have not been comprehensively identified. We employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout screens in primary CD4+ T cells to discover pro- and anti-HIV host factors systematically. Secondary pooled screens and individual perturbations validated high-confidence hits and revealed diverse mechanisms of action. CRISPRa uncovered multiple potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A. PI16 interacts with host factors involved in HIV fusion and inhibits viral entry, whereas PPID (Cyp40), a paralog of the proviral cyclophilin CypA, binds capsid and reduces nuclear import of the HIV core. Structural modeling, evolutionary analyses, and targeted mutagenesis revealed domains and residues required for PPID-mediated HIV restriction, including non-human primate ortholog substitutions that enhance antiviral activity. Together, these data define the functional HIV-host interaction landscape in primary human T cells and uncover new mechanisms modulating infection.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"24 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147732311","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

B cell deficiency limits exercise capacity by remodeling liver glutamate metabolism B细胞缺乏通过重塑肝脏谷氨酸代谢限制运动能力

IF 64.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.039

Youxiang Mao, Ziyan Xia, Xu Pan, Wenjun Xia, Peng Jiang

引用次数: 0

Gut microbiome is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade 肠道微生物组与接受辅助免疫检查点阻断的高危黑色素瘤切除患者的无复发生存率相关

IF 64.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.041

Mykhaylo Usyk, Richard B. Hayes, Rob Knight, Antonio Gonzalez, Huilin Li, Iman Osman, Jeffrey S. Weber, Jiyoung Ahn

{"title":"Gut microbiome is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade","authors":"Mykhaylo Usyk, Richard B. Hayes, Rob Knight, Antonio Gonzalez, Huilin Li, Iman Osman, Jeffrey S. Weber, Jiyoung Ahn","doi":"10.1016/j.cell.2026.03.041","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.041","url":null,"abstract":"Patients with resected, high-risk melanoma receive adjuvant immune checkpoint blockade (ICB), yet clinical benefit remains unpredictable, with 25%–40% of patients experiencing recurrence. To evaluate whether pre-treatment gut microbiome (GMB) features predict recurrence, we analyzed stool samples from 674 patients enrolled in a phase 3 clinical trial, CheckMate 915, which investigated the combination of nivolumab plus ipilimumab versus nivolumab as a single agent across five geographic regions. Region-specific and cross-region meta-analyses identified pre-treatment taxa associated with recurrence, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium. Recurrence prediction was strongest when the validation cohort exhibited GMB profiles similar to those in the discovery cohort. Among closely matched individuals (Jensen-Shannon divergence [JSD] ≤ 0.11), the area under the curve (AUC) for recurrence prediction ranged from 0.78 to 0.94 across regions. GMB composition remained largely stable following treatment. These findings suggest that gut bacterial markers can predict recurrence after adjuvant ICB treatment in melanoma, supporting their potential as clinically actionable biomarkers to guide personalized therapy.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"323 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708877","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

2'3'-cGAMP-induced membrane shearing promotes broad antiphage immunity 2'3'- cgamp诱导的膜剪切促进广泛的抗噬菌体免疫

IF 64.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.043

Yina Gao, Zhaolong Li, Yufei Zhou, Weimin Li, Quanjin Li, Jingge Wang, Miao Shi, Feng Ye, Chunqiu Zhao, Songqing Liu, Qiuyao Jiang, Yun Zhu, Fei Sun, Ang Gao, Pu Gao

{"title":"2'3'-cGAMP-induced membrane shearing promotes broad antiphage immunity","authors":"Yina Gao, Zhaolong Li, Yufei Zhou, Weimin Li, Quanjin Li, Jingge Wang, Miao Shi, Feng Ye, Chunqiu Zhao, Songqing Liu, Qiuyao Jiang, Yun Zhu, Fei Sun, Ang Gao, Pu Gao","doi":"10.1016/j.cell.2026.03.043","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.043","url":null,"abstract":"Cyclic-oligonucleotide-based anti-phage signaling system (CBASS), a central prokaryotic antiviral strategy and evolutionary ancestor of the mammalian cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, relies on cyclic-nucleotide-activated effectors to elicit immunity. The most prevalent effectors are transmembrane (TM) proteins, yet their mechanisms remain unknown. Here, we show how a representative three transmembrane (3TM)-SMODS-associated fused to various effector domains (SAVED) effector couples ligand sensing to membrane disruption. Upon binding 2'3'-cyclic GMP-AMP (cGAMP)—synthesized by bacterial cGAS/DncV-like nucleotidyltransferase (CD-NTase) with features resembling mammalian cGAS—3TM-SAVED assembles stepwise from an apo monomer through a transient dimer into extended filaments. Filament assembly employs 2'3'-cGAMP as molecular glue linking SAVED domains and reorients TM helices and amphipathic hairpins into vertically offset arrays. Both arrays bear opposing hydrophobic and hydrophilic faces, thereby driving vertical lipid shearing. This shearing generates a linear pore array that permeabilizes membranes and triggers cell death. These findings uncover the long-missing mechanism of CBASS TM effectors and establish vertical membrane shearing as an unrecognized principle of membrane disruption across domains of life.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"12 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708880","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 phytoscreen identifies a garlic compound as a deterrent of mating and egg laying in Drosophila and mosquitoes 植物筛选发现，一种大蒜化合物可以阻止果蝇和蚊子交配和产卵

IF 64.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.037

Shimaa A.M. Ebrahim, Gaëlle J.S. Talross, Hany K.M. Dweck, John J. Shepard, John R. Carlson

引用次数: 0

Predicting competition and substrate preferences for targeted microbiome alteration 预测目标微生物组改变的竞争和底物偏好

IF 64.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.036

Oriane Moyne, Grant J. Norton, Mahmoud Al-Bassam, Chloe Lieng, Deepan Thiruppathy, Manish Kumar, Eli Haddad, Yuhan Weng, Manuela Raffatellu, Livia S. Zaramela, Karsten Zengler

{"title":"Predicting competition and substrate preferences for targeted microbiome alteration","authors":"Oriane Moyne, Grant J. Norton, Mahmoud Al-Bassam, Chloe Lieng, Deepan Thiruppathy, Manish Kumar, Eli Haddad, Yuhan Weng, Manuela Raffatellu, Livia S. Zaramela, Karsten Zengler","doi":"10.1016/j.cell.2026.03.036","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.036","url":null,"abstract":"Microbiome science has greatly expanded our understanding of microbial life and its roles in the environment and human health. Yet microbiome science often relies on descriptive, correlation-based approaches that limit causal insight and intentional intervention designs. Moving toward predictive and mechanistic understanding requires functional characterization of microbial interactions and metabolic preferences. Here, we present microbial interaction and niche determination (MIND), which quantifies mRNA translation prioritization to infer substrate preferences and competitive interactions in complex communities. Applied to synthetic communities, soil, human fecal samples, and a mouse model, MIND predicted microbial competition and substrate preferences, guiding precision prebiotic and probiotic interventions to selectively modulate community composition. Currently focused on competition and substrate utilization, MIND could be further extended to capture additional interactions and ecological niches. By linking functional measurements to ecological outcomes, MIND offers a broadly applicable framework for targeted microbiome manipulation and rational intervention design rooted in functional insight.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708878","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

p53 safeguards chemical reprogramming of human somatic cells toward pluripotency. P53保护人类体细胞向多能性的化学重编程。

IF 42.5 1区生物学

Cell Pub Date : 2026-04-17 DOI: 10.1016/j.cell.2026.03.038

Lin Cheng, Yanglu Wang, Zhihan Yang, Jingxiao Cao, Fangqi Peng, Tianlong Lan, Ruoqi Cheng, Tianxing Liu, Ziqing Xia, Jingyang Guan, Cheng Li, Shicheng Sun, Hongkui Deng

{"title":"p53 safeguards chemical reprogramming of human somatic cells toward pluripotency.","authors":"Lin Cheng, Yanglu Wang, Zhihan Yang, Jingxiao Cao, Fangqi Peng, Tianlong Lan, Ruoqi Cheng, Tianxing Liu, Ziqing Xia, Jingyang Guan, Cheng Li, Shicheng Sun, Hongkui Deng","doi":"10.1016/j.cell.2026.03.038","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.038","url":null,"abstract":"Cell fate manipulation is powerful for generating desired cell types through reprogramming. However, reprogramming induces dramatic changes in cell states and identities, which can be risky, necessitating strict regulation to ensure safety and efficiency. p53 is essential for genome stability; however, it functionally opposes oncogenes comprising the Yamanaka factors. Delicately balancing p53 activity for efficient reprogramming has proven challenging. Here, we demonstrate that p53 is essential for chemical reprogramming, unlike its inhibitory role in transcription factor-mediated reprogramming. Unexpectedly, suppressing p53 impairs the generation of chemically induced pluripotent stem cells (CiPSCs). p53 prevents excessive epithelial-to-mesenchymal transition during the early reprogramming stages. Retinoic acid signaling activation promotes CiPSC generation by leveraging p53's anti-metastatic function via BTG2. Cell proliferation ability is sustained in the presence of p53 expression by regulating p21 with chemicals. p53 preservation shows practical advantages in securing genome integrity; thus, chemical reprogramming is promising for delicately balancing p53 activity and achieving efficient reprogramming for cell fate manipulation.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716099","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

Cell最新文献