Cell reports最新文献

Inward transport of organelles drives outward migration of the spindle during C. elegans meiosis.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-22 DOI: 10.1016/j.celrep.2025.115458

Alma P Aquino, Wenzhe Li, Aastha Lele, Denisa Lazureanu, Megan F Hampton, Rebecca M Do, Melissa C Lafrades, Maria G Barajas, Antonio A Batres, Francis J McNally

引用次数: 0

The Natural Compound Notopterol Binds and Targets JAK2/3 to Ameliorate Inflammation and Arthritis.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-21 DOI: 10.1016/j.celrep.2025.115519

Qiong Wang, Xin Zhou, Long Yang, Yongjian Zhao, Zhihuan Chew, Jun Xiao, Chang Liu, Xin Zheng, Yuxiao Zheng, Qi Shi, Qianqian Liang, Yongjun Wang, Hongyan Wang

引用次数: 0

The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-21 DOI: 10.1016/j.celrep.2025.115456

Diogo Fonseca-Pereira, Sena Bae, Slater L Clay, Monia Michaud, Meghan H MacDonald, Jonathan N Glickman, Wendy S Garrett

{"title":"The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function.","authors":"Diogo Fonseca-Pereira, Sena Bae, Slater L Clay, Monia Michaud, Meghan H MacDonald, Jonathan N Glickman, Wendy S Garrett","doi":"10.1016/j.celrep.2025.115456","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115456","url":null,"abstract":"Group 3 innate lymphoid cells (ILC3s) are tissue-resident cells that sense environmental cues, control infections, and promote tissue homeostasis at mucosal surfaces. The metabolic sensor liver kinase B1 (LKB1) integrates intracellular stress, metabolism, and mitochondrial function to promote the development and effector functions of a variety of immune cells; however, the role of LKB1 in ILC3 function was unknown. Here, we show that LKB1 is crucial for adult ILC3 homeostasis, cytokine production, and mitochondrial function. ILC3-specific LKB1 deletion resulted in a reduced number of ILC3s and interleukin-22 (IL-22) production. LKB1-deficient ILC3s had decreased survival, mitochondrial dysfunction, cytoplasmic lipid accumulation, and altered bioenergetics. Using LKB1 downstream kinase modulators, we found that LKB1 regulation of ILC3 survival and IL-22 production requires signaling through microtubule affinity-regulating kinases (MARKs). Mechanistically, LKB1 deficiency resulted in increased reactive oxygen species (ROS) production and NFAT2 and PD-1 expression. Our work reveals that metabolic regulation of enteric ILC3 function by an LKB1-dependent signaling network is crucial for intestinal immunity and tissue homeostasis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115456"},"PeriodicalIF":7.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691279","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

DSCC1 restrains 53BP1/RIF1 signaling at DNA double-strand breaks to promote homologous recombination repair.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-20 DOI: 10.1016/j.celrep.2025.115452

Jiaxin Tian, Jiaheng Li, Fengqi Liu, Cong Wang, Binghe Sun, Jin Yan, Bo Zhu, Yu Qin, Shentong Fang, Haoxing Zhang, Guo Chen

{"title":"DSCC1 restrains 53BP1/RIF1 signaling at DNA double-strand breaks to promote homologous recombination repair.","authors":"Jiaxin Tian, Jiaheng Li, Fengqi Liu, Cong Wang, Binghe Sun, Jin Yan, Bo Zhu, Yu Qin, Shentong Fang, Haoxing Zhang, Guo Chen","doi":"10.1016/j.celrep.2025.115452","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115452","url":null,"abstract":"Mammalian DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR) and non-homologous end joining (NHEJ). HR occurs in the S/G2 phase, while NHEJ dominates in G1 phase. 53BP1 promotes NHEJ by recruiting RIF1 to DSBs in G1, but its inhibition during S/G2 remains unclear. Here, we identify DNA replication and sister chromatid cohesion 1 (DSCC1) as a key regulator that antagonizes 53BP1/RIF1 signaling in a cell-cycle-dependent manner. ATR-mediated phosphorylation of DSCC1 at Thr181 leads to its recruitment to DSB sites and promotes HR by facilitating DNA end resection. During S/G2, E2F1-induced DSCC1 expression is phosphorylated by cyclin-dependent kinase 2 (CDK2), enabling DSCC1 to interact with 53BP1 and restrain ataxia telangiectasia mutated (ATM)-mediated 53BP1 phosphorylation, consequently preventing RIF1 recruitment. Pathologically, DSCC1 is elevated in ovarian cancer, conferring poly (ADP-ribose) polymerase (PARP) inhibitor resistance. Thus, DSCC1 plays a crucial role in DSB repair pathway choice toward HR repair during S/G2 phase, providing a potential target to optimize PARP inhibitor therapy in BRCA1/2-proficient cancers.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115452"},"PeriodicalIF":7.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673339","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 neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-20 DOI: 10.1016/j.celrep.2025.115467

Wenxiu Dai, Ximing Nian, Zhihao Zhou, Ailian Du, Qi Liu, Shufang Jia, Yan Lu, Daopeng Li, Xiaoyun Lu, Yanqin Zhu, Qiuying Huang, Jiaquan Lu, Yunshan Xiao, Liangkai Zheng, Wanying Lei, Nengyin Sheng, Xiujuan Zang, Yanqiang Hou, Zilong Qiu, Ren Xu, Shuhua Xu, Xueqin Zhang, Liang Zhang

{"title":"A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.","authors":"Wenxiu Dai, Ximing Nian, Zhihao Zhou, Ailian Du, Qi Liu, Shufang Jia, Yan Lu, Daopeng Li, Xiaoyun Lu, Yanqin Zhu, Qiuying Huang, Jiaquan Lu, Yunshan Xiao, Liangkai Zheng, Wanying Lei, Nengyin Sheng, Xiujuan Zang, Yanqiang Hou, Zilong Qiu, Ren Xu, Shuhua Xu, Xueqin Zhang, Liang Zhang","doi":"10.1016/j.celrep.2025.115467","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115467","url":null,"abstract":"Oligodendrocyte maturation arrest in hypoxia-induced white matter injury (WMI) results in long-term neurofunctional disabilities of preterm infants. Although neurons are closely linked to myelination regulation, how neurons respond to the above process remains elusive. Here, we identify a compensatory role of neuronal Slit1-dependent signaling in protecting against hypoxia-induced hypomyelination and ameliorating motor and cognitive disabilities. Conditional ablation of Slit1 in neurons exacerbates hypoxia-induced hypomyelination but is negligible for developmental myelination. Secreted Slit1 from hypoxic neurons directly targets oligodendrocyte, acting through Robo2-srGAP1-RhoA signaling. Pharmacological inhibition of RhoA restores myelination and promotes neurofunctional recovery in adolescent mice. Notably, natural selection analysis and functional validation indicate an adaptive variant with higher Slit1 gene expression in the Tibetan population, which has low oxygen availability. Collectively, these findings show a neuronal Slit1-dependent program of OL differentiation and suggest that targeting the Slit1-Robo2 signaling axis may have therapeutic potential for treatment of preterm infants with hypoxic WMI.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115467"},"PeriodicalIF":7.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673316","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

Integrated multi-omics profiling characterizes the crucial role of human dental epithelium during tooth development.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-20 DOI: 10.1016/j.celrep.2025.115437

Ran Zhang, Zongshan Shen, Zhenni Zhao, Xiuge Gu, Tianxing Yan, Wei Wei, Chuan Wu, Jinxuan Xia, Yuanyuan Zhang, Suwen Chen, Linsha Ma, Dong Zhang, Xiaoshan Wu, Paul T Sharpe, Songlin Wang

{"title":"Integrated multi-omics profiling characterizes the crucial role of human dental epithelium during tooth development.","authors":"Ran Zhang, Zongshan Shen, Zhenni Zhao, Xiuge Gu, Tianxing Yan, Wei Wei, Chuan Wu, Jinxuan Xia, Yuanyuan Zhang, Suwen Chen, Linsha Ma, Dong Zhang, Xiaoshan Wu, Paul T Sharpe, Songlin Wang","doi":"10.1016/j.celrep.2025.115437","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115437","url":null,"abstract":"The development of early human tooth primordia is not well understood. Here, we linked single-cell RNA sequencing, spatial transcriptomics, and secretome analysis to characterize human fetal tooth development over time. A spatiotemporal atlas of human tooth development at multiple levels was mapped, identifying previously uncharacterized epithelial subpopulations with distinct gene expression profiles and spatial localization. Dynamic changes in epithelial-mesenchymal interactions across developmental stages were characterized. Secretome analysis confirmed the extensive paracrine signaling from the epithelial to mesenchymal compartments and uncovered signaling factors produced by dental epithelium (DE) that regulate mesenchymal cell fate and differentiation. Integration of these datasets highlighted the crucial role of the DE in orchestrating tooth morphogenesis. Our multi-omics approach not only provides unprecedented insights into the cellular and molecular mechanisms of ectoderm-derived tissue development but also serves as a valuable resource, which is publicly available online, for future studies on human tooth regeneration and related diseases.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115437"},"PeriodicalIF":7.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691327","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 murine lung microbiome is disbalanced by the human-pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria. 人类致病真菌烟曲霉会导致小鼠肺部微生物群失衡，从而使厌氧菌大量繁殖。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-19 DOI: 10.1016/j.celrep.2025.115442

Liubov Nikitashina, Xiuqiang Chen, Lukas Radosa, Kexin Li, Maria Straßburger, Bastian Seelbinder, Wibke Böhnke, Sarah Vielreicher, Sandor Nietzsche, Thorsten Heinekamp, Ilse D Jacobsen, Gianni Panagiotou, Axel A Brakhage

{"title":"The murine lung microbiome is disbalanced by the human-pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria.","authors":"Liubov Nikitashina, Xiuqiang Chen, Lukas Radosa, Kexin Li, Maria Straßburger, Bastian Seelbinder, Wibke Böhnke, Sarah Vielreicher, Sandor Nietzsche, Thorsten Heinekamp, Ilse D Jacobsen, Gianni Panagiotou, Axel A Brakhage","doi":"10.1016/j.celrep.2025.115442","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115442","url":null,"abstract":"Here, we report significant changes in the composition of the lung microbiome and metabolome of mice under immune suppression, infection of immunosuppressed mice with virulent and avirulent strains of the clinically important human-pathogenic fungus Aspergillus fumigatus, and treatment with the clinically used antifungal drug voriconazole. Our data also indicate the important role of the gut microbiome for lung homeostasis mediated by the plasma metabolome. In the lung microbiome, DNA sequencing indicates that infection by A. fumigatus leads to a significant increase of anaerobic bacteria, most prominently of Ligilactobacillus murinus; the latter has been confirmed by qPCR analyses. We also isolated live bacteria, including L. murinus, from the murine lower respiratory tract. Co-cultivation of L. murinus and A. fumigatus leads to a reduction in oxygen concentration accompanied by an increase of L. murinus cells, suggesting that A. fumigatus establishes a microaerophilic niche, thereby promoting growth of anaerobic bacteria.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115442"},"PeriodicalIF":7.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669232","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

Activated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-19 DOI: 10.1016/j.celrep.2025.115425

Catherine A Nicholas, Fatima A Tensun, Spencer A Evans, Kevin P Toole, Jessica E Prendergast, Hali Broncucia, Jay R Hesselberth, Peter A Gottlieb, Kristen L Wells, Mia J Smith

{"title":"Activated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes.","authors":"Catherine A Nicholas, Fatima A Tensun, Spencer A Evans, Kevin P Toole, Jessica E Prendergast, Hali Broncucia, Jay R Hesselberth, Peter A Gottlieb, Kristen L Wells, Mia J Smith","doi":"10.1016/j.celrep.2025.115425","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115425","url":null,"abstract":"Autoreactive B cells play an important but ill-defined role in autoimmune type 1 diabetes (T1D). We isolated pancreatic islet antigen-reactive B cells from the peripheral blood of non-diabetic autoantibody-negative first-degree relatives, autoantibody-positive, and recent-onset T1D donors. Single-cell RNA sequencing analysis revealed that islet antigen-reactive B cells from autoantibody-positive and T1D donors had altered gene expression in pathways associated with B cell signaling and inflammation. Additionally, BCR sequencing uncovered a similar shift in islet antigen-reactive B cell repertoires among autoantibody-positive and T1D donors where greater clonal expansion was also observed. Notably, a substantial fraction of islet antigen-reactive B cells in autoantibody-positive and T1D donors appeared to be polyreactive, which was corroborated by analysis of recombinant monoclonal antibodies. These results expand our understanding of autoreactive B cell phenotypes during T1D and identify unique BCR repertoire changes that may serve as biomarkers for increased disease risk.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115425"},"PeriodicalIF":7.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673321","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

Random compressed coding with neurons. 神经元随机压缩编码

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-18 DOI: 10.1016/j.celrep.2025.115412

Simone Blanco Malerba, Mirko Pieropan, Yoram Burak, Rava Azeredo da Silveira

引用次数: 0

Hi-C profiling in tissues reveals 3D chromatin-regulated breast tumor heterogeneity informing a looping-mediated therapeutic avenue. 组织中的 Hi-C 图谱揭示了三维染色质调控的乳腺肿瘤异质性，为循环介导的治疗途径提供了信息。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-18 DOI: 10.1016/j.celrep.2025.115450

Lavanya Choppavarapu, Kun Fang, Tianxiang Liu, Aigbe G Ohihoin, Victor X Jin

{"title":"Hi-C profiling in tissues reveals 3D chromatin-regulated breast tumor heterogeneity informing a looping-mediated therapeutic avenue.","authors":"Lavanya Choppavarapu, Kun Fang, Tianxiang Liu, Aigbe G Ohihoin, Victor X Jin","doi":"10.1016/j.celrep.2025.115450","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115450","url":null,"abstract":"The limitations of Hi-C (high-throughput chromosome conformation capture) profiling in in vitro cell culture include failing to recapitulate disease-specific physiological properties and lacking a clinically relevant disease microenvironment. In this study, we conduct Hi-C profiling in a pilot cohort of 12 breast tissues comprising two normal tissues, five ER+ breast primary tumors, and five tamoxifen-treated recurrent tumors. We demonstrate 3D chromatin-regulated breast tumor heterogeneity and identify a looping-mediated target gene, CA2, which might play a role in driving tamoxifen resistance. The inhibition of CA2 impedes tumor growth both in vitro and in vivo and reverses chromatin looping. The disruption of CA2 looping reduces tamoxifen-resistant cancer cell proliferation, decreases CA2 mRNA and protein expression, and weakens the looping interaction. Our study thus provides mechanistic and functional insights into the role of 3D chromatin architecture in regulating breast tumor heterogeneity and informs a new looping-mediated therapeutic avenue for treating breast cancer.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115450"},"PeriodicalIF":7.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669233","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