Cell reports最新文献_第2页

Bilirubin metabolism in the liver orchestrates antiviral innate immunity in the body.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115481

Qian Du, Wei He, Xiangjie Chen, Jin Liu, Mingcheng Guan, Yichang Chen, Meixia Chen, Yukang Yuan, Yibo Zuo, Ying Miao, Qin Wang, Haiyan Zhou, Yanli Liu, Jingting Jiang, Hui Zheng

{"title":"Bilirubin metabolism in the liver orchestrates antiviral innate immunity in the body.","authors":"Qian Du, Wei He, Xiangjie Chen, Jin Liu, Mingcheng Guan, Yichang Chen, Meixia Chen, Yukang Yuan, Yibo Zuo, Ying Miao, Qin Wang, Haiyan Zhou, Yanli Liu, Jingting Jiang, Hui Zheng","doi":"10.1016/j.celrep.2025.115481","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115481","url":null,"abstract":"Bilirubin metabolism crucially maintains normal liver function, but whether it contributes to antiviral immunity remains unknown. Here, we reveal that the liver bilirubin metabolic pathway facilitates antiviral innate immunity of the body. We discovered that viral infection upregulates uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression in the liver, which in turn stabilizes IRF3 proteins to promote type I interferon (IFN-I) production. Moreover, we found that serum unconjugated bilirubin (UCB), a unique physiological substrate of UGT1A1, can competitively inhibit the binding of IFN-I to IFN-I receptor 2 (IFNAR2), thus attenuating IFN-I-induced antiviral signaling of the body. Accordingly, effective bilirubin metabolism in the liver promotes antiviral immunity of the body by specifically employing liver UGT1A1-mediated enhancement of IFN-I production and reducing serum bilirubin-mediated inhibition of IFN-I signaling. This study uncovers the significance of bilirubin metabolism in antiviral innate immunity and demonstrates that conventional IFN-I therapy is less efficient for patients with hepatitis B virus (HBV) with high levels of bilirubin.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115481"},"PeriodicalIF":7.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735595","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

Orchestration of pluripotent stem cell genome reactivation during mitotic exit.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115486

Silja Placzek, Ludovica Vanzan, Cédric Deluz, David M Suter

引用次数: 0

The impact of Coronavirus Nsp1 on host mRNA degradation is independent of its role in translation inhibition.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115488

Emilie Bäumlin, Dominic Andenmatten, Jonas Luginbühl, Aurélien Lalou, Nino Schwaller, Evangelos D Karousis

{"title":"The impact of Coronavirus Nsp1 on host mRNA degradation is independent of its role in translation inhibition.","authors":"Emilie Bäumlin, Dominic Andenmatten, Jonas Luginbühl, Aurélien Lalou, Nino Schwaller, Evangelos D Karousis","doi":"10.1016/j.celrep.2025.115488","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115488","url":null,"abstract":"When host cells are infected with coronaviruses, the first viral protein produced is non-structural protein 1 (Nsp1). This protein inhibits host protein synthesis and induces host mRNA degradation to enhance viral proliferation. Despite its critical role, the mechanism by which Nsp1 mediates cellular mRNA degradation remains unclear. In this study, we use cell-free translation to address how host mRNA stability is regulated by Nsp1. We reveal that SARS-CoV-2 Nsp1 binding to the ribosome is enough to trigger mRNA degradation independently of ribosome collisions or active translation. MERS-CoV Nsp1 inhibits translation without triggering degradation, highlighting mechanistic differences between the two Nsp1 counterparts. Nsp1 and viral mRNAs appear to co-evolve, rendering viral mRNAs immune to Nsp1-mediated degradation in SARS-CoV-2, MERS-CoV, and Bat-Hp viruses. By providing insights into the mode of action of Nsp1, our study helps to understand the biology of Nsp1 better and find strategies for therapeutic targeting against coronaviral infections.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115488"},"PeriodicalIF":7.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735653","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

Neural correlates of visual object recognition in rats.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115461

Juliana Y Rhee, César Echavarría, Edward Soucy, Joel Greenwood, Javier A Masís, David D Cox

引用次数: 0

Presynaptic recycling pool density regulates spontaneous synaptic vesicle exocytosis rate and is upregulated in the presence of β-amyloid.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115410

Paxton Wilson, Noah Kim, Rachel Cotter, Mason Parkes, Luca Cmelak, Miranda N Reed, Michael W Gramlich

{"title":"Presynaptic recycling pool density regulates spontaneous synaptic vesicle exocytosis rate and is upregulated in the presence of β-amyloid.","authors":"Paxton Wilson, Noah Kim, Rachel Cotter, Mason Parkes, Luca Cmelak, Miranda N Reed, Michael W Gramlich","doi":"10.1016/j.celrep.2025.115410","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115410","url":null,"abstract":"Synapses represent a fundamental unit of information transfer during cognition via presynaptic vesicle exocytosis. It has been established that evoked release is probabilistic, but the mechanisms behind spontaneous release are less clear. Understanding spontaneous release is vital, as it plays a key role in maintaining synaptic connections. We propose a model framework for spontaneous release where the reserve pool geometrically constrains recycling pool vesicles, creating an entropic force that drives spontaneous release rate. We experimentally support this framework using SEM, fluorescence microscopy, computational modeling, and pharmacological approaches. Our model correctly predicts the spontaneous release rate as a function of presynapse size. Finally, we use our approach to show how β-amyloid mutations linked to Alzheimer's disease lead to increased spontaneous release rates. These results indicate that synapses regulate the density of the recycling pool to control the spontaneous release rate and may serve as an early indicator of Alzheimer's disease.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115410"},"PeriodicalIF":7.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728993","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

Oncogenic properties of wild-type DNA repair gene FANCA in breast cancer.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115480

Liang Luo, Fenghua Yuan, Anna Palovcak, Fang Li, Qingqi Yuan, Daniel Calkins, Zoe Manalo, Yan Li, Dazhi Wang, Mike Zhou, Catherine Zhou, Matthew Li, Yuan-De Tan, Feng Bai, Yuguang Ban, Christian Mason, Evan Roberts, Daniel Bilbao, Zhao-Jun Liu, Karoline Briegel, Scott M Welford, Xin-Hai Pei, Sylvia Daunert, Wenjun Liu, Yanbin Zhang

{"title":"Oncogenic properties of wild-type DNA repair gene FANCA in breast cancer.","authors":"Liang Luo, Fenghua Yuan, Anna Palovcak, Fang Li, Qingqi Yuan, Daniel Calkins, Zoe Manalo, Yan Li, Dazhi Wang, Mike Zhou, Catherine Zhou, Matthew Li, Yuan-De Tan, Feng Bai, Yuguang Ban, Christian Mason, Evan Roberts, Daniel Bilbao, Zhao-Jun Liu, Karoline Briegel, Scott M Welford, Xin-Hai Pei, Sylvia Daunert, Wenjun Liu, Yanbin Zhang","doi":"10.1016/j.celrep.2025.115480","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115480","url":null,"abstract":"FANCA is one of the 23 genes whose deficiencies lead to defective DNA interstrand crosslink repair and cancer-prone Fanconi anemia disease. Beyond its functions in DNA repair and tumor suppression, we report that high FANCA expression is strongly associated with breast cancer development. Overexpression of WT-FANCA significantly promotes breast cancer cell proliferation and tumor growth both in vitro and in vivo, while FANCA deficiency severely compromises the proliferation of breast cancer cells, but not non-tumorigenic breast epithelial cells. Heterozygous knockout of FANCA in breast cancer mouse models is sufficient to cause significant reduction of breast tumor growth in vivo. Furthermore, we have shown that high FANCA expression in breast cancer correlates with promoter hypomethylation in a TET-dependent manner, and TET inhibition recapitulates the proliferation defects caused by FANCA deficiency. Our study identifies the oncogenic properties of WT-FANCA and shows that FANCA is a promising target for breast cancer intervention.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115480"},"PeriodicalIF":7.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728988","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-metabolism-focused CRISPR screens identify enzymes of the mevalonate pathway as essential for prostate cancer growth.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115470

Gio Fidelito, Izabela Todorovski, Leonie Cluse, Stephin J Vervoort, Renea A Taylor, Matthew J Watt

{"title":"Lipid-metabolism-focused CRISPR screens identify enzymes of the mevalonate pathway as essential for prostate cancer growth.","authors":"Gio Fidelito, Izabela Todorovski, Leonie Cluse, Stephin J Vervoort, Renea A Taylor, Matthew J Watt","doi":"10.1016/j.celrep.2025.115470","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115470","url":null,"abstract":"Dysregulated lipid metabolism plays an important role in prostate cancer, although the understanding of the essential regulatory processes in tumorigenesis is incomplete. We employ a CRISPR-Cas9 screen using a custom human lipid metabolism knockout library to identify essential genes for prostate cancer survival. Screening in three prostate cancer cell lines reveals 63 shared dependencies, with enrichment in terpenoid backbone synthesis and N-glycan biosynthesis. Independent knockout of key genes of the mevalonate pathway reduces cell proliferation. Further investigation focuses on NUS1, a subunit of cis-prenyltransferase required for dolichol synthesis. NUS1 knockout decreases tumor growth in vivo and viability in patient-derived xenograft (PDX)-derived organoids. Mechanistic studies reveal that loss of NUS1 promotes oxidative stress, lipid peroxidation and ferroptosis sensitivity, endoplasmic reticulum (ER) stress, and G1 cell-cycle arrest, and it dampens androgen receptor (AR) signaling, collectively leading to growth arrest. This study highlights the critical role of the mevalonate-dolichol-N-glycan biosynthesis pathway, particularly NUS1, in prostate cancer survival and growth.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115470"},"PeriodicalIF":7.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728973","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

Homeostatic regulation of nucleoporins is a central driver of nuclear pore biogenesis.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115468

Stephen Sakuma, Marcela Raices, Ethan Y S Zhu, Dana Mamriev, Charles I Fisher, Susanne Heynen-Genel, Maximiliano A D'Angelo

{"title":"Homeostatic regulation of nucleoporins is a central driver of nuclear pore biogenesis.","authors":"Stephen Sakuma, Marcela Raices, Ethan Y S Zhu, Dana Mamriev, Charles I Fisher, Susanne Heynen-Genel, Maximiliano A D'Angelo","doi":"10.1016/j.celrep.2025.115468","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115468","url":null,"abstract":"Nuclear pore complexes (NPCs) are channels that control access to the genome. The number of NPCs that cells assemble varies between different cell types and in disease. However, the mechanisms regulating NPC formation in mammalian cells remain unclear. Using a genome-wide small interfering RNA (siRNA) screen, we identify translation-related factors, proteasome components, and the CCR4-NOT complex as top regulators of NPC assembly and numbers. While inhibition of ribosomal function and protein translation reduces NPC formation, blocking protein degradation or CCR4-NOT function increases NPC numbers. We demonstrate that CCR4-NOT inhibition raises global mRNA levels, increasing the pool of nucleoporin mRNAs available for translation. Upregulation of nucleoporin complexes in CCR4-NOT-inhibited cells allows for higher NPC formation, increasing total NPC numbers in normal and cancer cells. Our findings uncover that nucleoporin mRNA stability and protein homeostasis are major determinants of NPC formation and highlight a role for the CCR4-NOT complex in negatively regulating NPC assembly.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115468"},"PeriodicalIF":7.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763188","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

iMetAct: An integrated systematic inference of metabolic activity for dissecting tumor metabolic preference and tumor-immune microenvironment.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-06 DOI: 10.1016/j.celrep.2025.115375

Binxian Wang, Chao Huang, Xuan Liu, Zhenni Liu, Yilei Zhang, Wei Zhao, Qiuran Xu, Ping-Chih Ho, Zhengtao Xiao

{"title":"iMetAct: An integrated systematic inference of metabolic activity for dissecting tumor metabolic preference and tumor-immune microenvironment.","authors":"Binxian Wang, Chao Huang, Xuan Liu, Zhenni Liu, Yilei Zhang, Wei Zhao, Qiuran Xu, Ping-Chih Ho, Zhengtao Xiao","doi":"10.1016/j.celrep.2025.115375","DOIUrl":"10.1016/j.celrep.2025.115375","url":null,"abstract":"Metabolic enzymes play a central role in cancer metabolic reprogramming, and their dysregulation creates vulnerabilities that can be exploited for therapy. However, accurately measuring metabolic enzyme activity in a high-throughput manner remains challenging due to the complex, multi-layered regulatory mechanisms involved. Here, we present iMetAct, a framework that integrates metabolic-transcription networks with an information propagation strategy to infer enzyme activity from gene expression data. iMetAct outperforms expression-based methods in predicting metabolite conversion rates by accounting for the effects of post-translational modifications. With iMetAct, we identify clinically significant subtypes of hepatocellular carcinoma with distinct metabolic preferences driven by dysregulated enzymes and metabolic regulators acting at both the transcriptional and non-transcriptional levels. Moreover, applying iMetAct to single-cell RNA sequencing data allows for the exploration of cancer cell metabolism and its interplay with immune regulation in the tumor microenvironment. An accompanying online platform further facilitates tumor metabolic analysis, patient stratification, and immune microenvironment characterization.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115375"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575696","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

Modular mechanisms of immune priming and growth inhibition mediated by plant effector-triggered immunity.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-08 DOI: 10.1016/j.celrep.2025.115394

Himanshu Chhillar, Hoang Hung Nguyen, Pei-Min Yeh, Jonathan D G Jones, Pingtao Ding

引用次数: 0