Cell reports最新文献_第3页

Histone H3K27 methylation states are sequentially catalyzed in cycling cells. 组蛋白H3K27甲基化状态在循环细胞中被顺序催化。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118149

Jacob E Greene, Kami Ahmad, Steven Henikoff

引用次数: 0

Structural basis for cross-alphaherpesvirus neutralization by an antibody targeting a conserved hotspot on glycoprotein B. 针对糖蛋白B保守热点的抗体中和交叉α疱疹病毒的结构基础。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118158

Yu Li, Chengyu Yang, Guosong Wang, Yue Zeng, Kaiyun Chen, Yuchen Jiang, Mingmin Kang, Tian Chen, Mengxuan Gui, Mihnea Bostina, Shaowei Li, Ningshao Xia, Yixin Chen, Qingbing Zheng

{"title":"Structural basis for cross-alphaherpesvirus neutralization by an antibody targeting a conserved hotspot on glycoprotein B.","authors":"Yu Li, Chengyu Yang, Guosong Wang, Yue Zeng, Kaiyun Chen, Yuchen Jiang, Mingmin Kang, Tian Chen, Mengxuan Gui, Mihnea Bostina, Shaowei Li, Ningshao Xia, Yixin Chen, Qingbing Zheng","doi":"10.1016/j.celrep.2026.118158","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118158","url":null,"abstract":"Alphaherpesviruses, including herpes simplex viruses (HSV-1/2) and pseudorabies virus (PRV), pose significant threats to human and animal health, yet broad-spectrum interventions remain elusive. Here, we characterize C12A6, a neutralizing antibody (nAb) targeting glycoprotein B (gB) that cross-neutralizes HSV-1, HSV-2, and PRV and confers substantial, although incomplete, therapeutic protection against lethal HSV-1 or PRV infection. Cryo-electron microscopy structures of C12A6 in complex with PRV gB and HSV-2 gB reveal that the antibody engages a conserved conformational epitope on Domain I (DI). A conserved interaction framework, anchored by invariant polar contacts and a hydrophobic core, supports recognition across divergent alphaherpesvirus gBs. Comparison with the broader alphaherpesvirus antibody 16F9 shows that C12A6 additionally engages less-conserved peripheral residues, providing a structural basis for its more restricted recognition breadth. These findings define the structural basis for C12A6-mediated cross-neutralization and illuminate the functional architecture of gB DI as a target for broad-spectrum antiviral development.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118158"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191608","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

Neoplastic and non-neoplastic astrocyte states converge on mesenchymal and injury-response programs during glioblastoma recurrence. 在胶质母细胞瘤复发期间，肿瘤和非肿瘤星形细胞状态集中在间质和损伤反应程序上。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118119

David Lindgren, Rebecca Rosberg, Karolina I Smolag, Elinn Johansson, Sebastian Braun, Jonas Sjölund, Dimitra Manou, Enrico Pracucci, Bengt Phung, Katja Harbst, Pauline Jeannot, Yu Ching So, Paulina Bolivar, Maria Malmberg, Crister Ceberg, Johan Bengzon, Henrik Ahlenius, Göran B Jönsson, Kristian Pietras, Alexander Pietras

{"title":"Neoplastic and non-neoplastic astrocyte states converge on mesenchymal and injury-response programs during glioblastoma recurrence.","authors":"David Lindgren, Rebecca Rosberg, Karolina I Smolag, Elinn Johansson, Sebastian Braun, Jonas Sjölund, Dimitra Manou, Enrico Pracucci, Bengt Phung, Katja Harbst, Pauline Jeannot, Yu Ching So, Paulina Bolivar, Maria Malmberg, Crister Ceberg, Johan Bengzon, Henrik Ahlenius, Göran B Jönsson, Kristian Pietras, Alexander Pietras","doi":"10.1016/j.celrep.2026.118119","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118119","url":null,"abstract":"Glioblastomas initially respond to radiotherapy but invariably recur, often within high-dose radiation treatment fields. Although stromal radiation responses are incompletely understood, evidence suggests that the tumor microenvironment becomes tumor-supportive after therapy. Using a genetically engineered glioblastoma mouse model, we profiled healthy brain, primary tumors, and post-radiotherapy recurrences with single-cell and spatial transcriptomics and immunofluorescence. Across 13 non-neoplastic cell types and 10 tumor cell states, we mapped transcriptional adaptations accompanying progression from healthy brain to primary and recurrent glioblastoma. We find distinct astrocyte states linked to disease stage, including reactive, non-neoplastic astrocytes and tumor cells adopting reactive astrocyte-like phenotypes. Reactive astrocyte-like tumor cells with mesenchymal and injury-response signatures are enriched after radiotherapy and persist in recurrent tumors. Receptor-ligand interactions between reactive astrocytes and tumor cells include known and putative drivers of aggressiveness. These findings highlight convergent reactive astrocyte programs in astrocytes and tumor cells as potential mediators of glioblastoma radioresistance.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118119"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206584","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

Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning. 抑制右背外侧前额叶皮层选择性地增强无监督统计学习。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118123

Orsolya Pesthy, Zsuzsanna Viktória Pesthy, Teodóra Vékony, Karolina Janacsek, Dániel Fabó, Dezso Nemeth

{"title":"Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning.","authors":"Orsolya Pesthy, Zsuzsanna Viktória Pesthy, Teodóra Vékony, Karolina Janacsek, Dániel Fabó, Dezso Nemeth","doi":"10.1016/j.celrep.2026.118123","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118123","url":null,"abstract":"The brain must balance the automatic extraction of regularities with top-down cognitive control, yet the hemispheric contributions of the dorsolateral prefrontal cortex (DLPFC) remain unresolved. Here, we applied inhibitory repetitive transcranial magnetic stimulation to the left, right, or bilateral DLPFC in 95 adults during a probabilistic sequence learning task. We found that inhibiting the right and bilateral DLPFC enhanced statistical learning compared to sham stimulation. Contrary to the hypothesis that interference from existing knowledge would mediate this effect, episodic memory performance was unaffected. As an alternative, we propose that right DLPFC inhibition shifts cognitive processing toward an exploratory information-sampling strategy, supported by our finding of greater reaction time variability in the right and bilateral stimulation groups. Our results provide causal evidence for a right-lateralized suppressive influence of the DLPFC on unsupervised learning and suggest that its role is linked to information-processing style rather than direct competition with episodic memory systems.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118123"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191611","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

Peptide signaling in the paraventricular thalamus is essential for disrupted adult reward behaviors consequent to early-life adversity. 室旁丘脑中的肽信号对于早期生活逆境导致的成人奖励行为中断至关重要。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118142

Amalia Floriou-Servou, Ryan Weber, Yuncai Chen, Madison R Tetzlaff, Cassandra L Kooiker, Matthew T Birnie, Annabel K Short, Roshae C Roberts, Heidi Y Liang, Magdalena Gantuz, Mason Hardy, Nicholas Justice, Ali Mortazavi, Tallie Z Baram

{"title":"Peptide signaling in the paraventricular thalamus is essential for disrupted adult reward behaviors consequent to early-life adversity.","authors":"Amalia Floriou-Servou, Ryan Weber, Yuncai Chen, Madison R Tetzlaff, Cassandra L Kooiker, Matthew T Birnie, Annabel K Short, Roshae C Roberts, Heidi Y Liang, Magdalena Gantuz, Mason Hardy, Nicholas Justice, Ali Mortazavi, Tallie Z Baram","doi":"10.1016/j.celrep.2026.118142","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118142","url":null,"abstract":"Early-life adversity (ELA) is strongly linked to emotional disorders characterized by dysregulated reward behaviors. However, the mechanisms by which transient neonatal experiences generate enduring, sex-specific alterations in brain function remain unresolved. Paraventricular thalamus (PVT) neurons are selectively activated during ELA and contribute to disrupted adult reward behaviors. Here, we explore the molecular mechanisms behind these enduring, sex-specific disruptions. Combining activity-dependent genetic labeling with translating ribosome affinity purification, we find distinct gene translation programs in ELA and control mice of both sexes. Notably, the receptor for the neuropeptide corticotropin-releasing hormone receptor type 1 (Crhr1), is differentially expressed across rearing and sex in response to reward. CRISPR-Cas9-mediated Crhr1 deletion exclusively in early-life-activated PVT neurons normalizes reward behaviors in both male and female adult ELA mice. Thus, CRHR1 signaling in adult PVT neurons activated by ELA is a required and potentially targetable mechanism underlying sex-specific, ELA-induced disruptions of reward behaviors.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118142"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179555","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

NONO mitigates transcription-replication conflicts during replication stress by restraining BRD4-dependent transcription elongation. NONO通过抑制brd4依赖的转录延伸来减轻复制应激期间的转录-复制冲突。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118159

Wenchi Wu, Chengyan Ding, Jiameng Ma, Chao Li, Feng Long, Zhiyuan Feng, Cuiling Wang, Kaiping Hou, Jiawei Liu, Haoyuan Luo, Tengfei Yu, Duhan Zeng, Dan Wang, Xiaohua Wu, Jian-Hua Wang, Xingzhi Xu, Hailong Wang

{"title":"NONO mitigates transcription-replication conflicts during replication stress by restraining BRD4-dependent transcription elongation.","authors":"Wenchi Wu, Chengyan Ding, Jiameng Ma, Chao Li, Feng Long, Zhiyuan Feng, Cuiling Wang, Kaiping Hou, Jiawei Liu, Haoyuan Luo, Tengfei Yu, Duhan Zeng, Dan Wang, Xiaohua Wu, Jian-Hua Wang, Xingzhi Xu, Hailong Wang","doi":"10.1016/j.celrep.2026.118159","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118159","url":null,"abstract":"Transcription-replication conflicts (TRCs) drive genomic instability and are linked to tumorigenesis and treatment response. Replication stress exacerbates TRCs, but how cells coordinate transcription and replication to limit these conflicts remains unclear. Here, we identify NONO as a key regulator that maintains transcription-replication balance via BRD4 under replication stress. Replication stress triggers NONO acetylation at K243, enhancing BRD4 binding. On single-stranded DNA, NONO-BRD4 form condensates that block paused RNA polymerase II (RNAP2) release, fine-tuning elongation. NONO loss causes aberrant accumulation of elongating RNAP2 at termination regions, promoting TRCs and genomic instability. Conditions that increase origin firing, including ATR inhibition or BRCA2 deficiency, further exacerbate this phenotype in NONO-deficient cells, leading to pronounced synthetic lethality. Together, these findings define a NONO-mediated surveillance mechanism that couples replication stress to transcriptional restraint via condensate-dependent regulation of BRD4, and identify NONO as a potential therapeutic target in replication stress-driven cancers.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118159"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179519","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 NuRD complex shapes RNA polymerase III activity at highly expressed tRNA gene clusters, tuning the dynamic range of cellular tRNA pools. NuRD复合物在高表达tRNA基因簇上塑造RNA聚合酶III的活性，调节细胞tRNA池的动态范围。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118133

Ruiying Cheng, Rajendra K C, Simon Lizarazo, Junmeng Yuan, Sihang Zhou, Saindhabi Ghosh, Kevin Van Bortle

{"title":"The NuRD complex shapes RNA polymerase III activity at highly expressed tRNA gene clusters, tuning the dynamic range of cellular tRNA pools.","authors":"Ruiying Cheng, Rajendra K C, Simon Lizarazo, Junmeng Yuan, Sihang Zhou, Saindhabi Ghosh, Kevin Van Bortle","doi":"10.1016/j.celrep.2026.118133","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118133","url":null,"abstract":"RNA polymerase III (Pol III) transcription produces RNAs involved in core biological processes and is therefore coupled to fluctuating demands for protein synthesis and cell growth. However, the mechanisms underlying dynamic Pol III regulation remain incompletely understood. To address this gap, we investigated protein-protein interactions shared across multiple Pol III subunits to characterize the macromolecular interactome of Pol III, with special attention directed toward potential regulatory factors. Our survey uncovers interactions between Pol III and the NuRD (nucleosome remodeling and deacetylase) complex. We further show that NuRD localizes to active Pol III-transcribed genes, including tRNA gene clusters associated with notably high expression. Inhibiting NuRD-associated deacetylase activity increases Pol III transcription at these sites, suggesting that NuRD constrains Pol III activity and thereby modulates the dynamic range of Pol III-derived RNAs. These findings implicate NuRD as a chromatin-based mechanism linking signaling events and metabolic need with the dynamic availability of specific tRNA pools.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118133"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191670","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

Lipid droplet targeting drives substrate access during very long chain fatty acid activation by Fat1. 脂滴靶向驱动了长链脂肪酸被Fat1激活过程中的底物通路。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118150

Carolin Willner, Jennifer Sapia, Bianca M Esch, Giovanna Nuccetelli, Pia Erdbrügger, Lisa Kauffmann, Alicia Damm, Sergej Limar, Sebastian Eising, Stefan Walter, Abdou Rachid Thiam, Carolin Körner, Stefano Vanni, Florian Fröhlich

{"title":"Lipid droplet targeting drives substrate access during very long chain fatty acid activation by Fat1.","authors":"Carolin Willner, Jennifer Sapia, Bianca M Esch, Giovanna Nuccetelli, Pia Erdbrügger, Lisa Kauffmann, Alicia Damm, Sergej Limar, Sebastian Eising, Stefan Walter, Abdou Rachid Thiam, Carolin Körner, Stefano Vanni, Florian Fröhlich","doi":"10.1016/j.celrep.2026.118150","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118150","url":null,"abstract":"Fatty acids require conjugation with coenzyme A (CoA) for their incorporation into membrane lipids. Of these, very-long-chain fatty acids (VLCFAs), the precursors of yeast ceramides, are particularly hydrophobic. Yet, it remains unresolved where and how the sole VLCFA-CoA synthetase Fat1 activates them. Here, we show that lipid droplets (LDs) are both the site of free VLCFA storage and their place of activation. Free VLCFAs preferentially partition into LDs in molecular simulations and in vitro reconstitutions, whereas Fat1 targets the LD surface in cells via an N-terminal amphipathic helix. Structural predictions identify an essential hydrophobic cavity in Fat1 that connects the active site to the membrane, suggesting that VLCFAs shuttle directly from the LD core into the enzymatic pocket. Our model explains how the organelle targeting of a fatty acid activator evolved to match the biophysical properties, and consequently, the subcellular localization of its highly hydrophobic substrate.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118150"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179505","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

Mitochondrial stress induces transcription of cytosolic and mitochondrial protein synthesis components via NHR-180. 线粒体应激通过NHR-180诱导胞质和线粒体蛋白合成组分的转录。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-14 DOI: 10.1016/j.celrep.2026.118161

Avijit Mallick, Theresa Ramalho, Levi Ali, Yunguang Du, Duy Hoang, Rui Li, Pooja Rai, Sookyung Kim, Rakeyah Ahsan, Ala M Shaqra, Andreas Bergmann, Celia A Schiffer, Lihua Julie Zhu, Brian Kelch, Kuang Shen, Cole M Haynes

{"title":"Mitochondrial stress induces transcription of cytosolic and mitochondrial protein synthesis components via NHR-180.","authors":"Avijit Mallick, Theresa Ramalho, Levi Ali, Yunguang Du, Duy Hoang, Rui Li, Pooja Rai, Sookyung Kim, Rakeyah Ahsan, Ala M Shaqra, Andreas Bergmann, Celia A Schiffer, Lihua Julie Zhu, Brian Kelch, Kuang Shen, Cole M Haynes","doi":"10.1016/j.celrep.2026.118161","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118161","url":null,"abstract":"The mitochondrial unfolded protein response (UPRmt), which promotes mitochondrial biogenesis and proteostasis, is regulated by the transcription factor ATFS-1. In C. elegans, impaired atfs-1 expression perturbs mitochondrial function and slows development. Here, using an RNAi suppressor screen, we find that inhibition of the nuclear hormone receptor NHR-180 increases mitochondrial function and developmental rate in atfs-1(null) worms. NHR-180 levels increase and become more nuclear-localized during mitochondrial dysfunction, inducing transcription of genes required for protein synthesis on cytosolic and mitochondrial ribosomes. The NHR-180 ligand-binding domain interacts with AMP, suggesting that NHR-180 may link cellular energy status to protein synthesis during mitochondrial stress. However, NHR-180-dependent activity is associated with exacerbated mitochondrial dysfunction. Consistent with these findings, inhibition of the S6 kinase homolog RSKS-1 increases mitochondrial function in atfs-1(null) worms. S6 kinase inhibition also increases respiration and mitochondrial DNA (mtDNA) content in mammalian ATF5-knockout cells and oxidative phosphorylation (OXPHOS)-deficient models.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118161"},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179604","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

Human organ chip models recapitulate FRC-driven high endothelial venule differentiation, immune recruitment, and cancer-induced disruption. 人体器官芯片模型概括了frc驱动的高内皮小静脉分化、免疫募集和癌症诱导的破坏。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118146

Elizabeth Oh, Esak Lee

引用次数: 0