Cell reports最新文献_第4页

Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease. 抗疱疹tau通过cGAS-STING-TBK1通路在阿尔茨海默病中保存神经元。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-02 DOI: 10.1016/j.celrep.2024.115109

Vanesa R Hyde, Chaoming Zhou, Juan R Fernandez, Krishnashis Chatterjee, Pururav Ramakrishna, Amanda Lin, Gregory W Fisher, Orhan Tunç Çeliker, Jill Caldwell, Omer Bender, Peter Joseph Sauer, Jose Lugo-Martinez, Daniel Z Bar, Leonardo D'Aiuto, Or A Shemesh

{"title":"Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.","authors":"Vanesa R Hyde, Chaoming Zhou, Juan R Fernandez, Krishnashis Chatterjee, Pururav Ramakrishna, Amanda Lin, Gregory W Fisher, Orhan Tunç Çeliker, Jill Caldwell, Omer Bender, Peter Joseph Sauer, Jose Lugo-Martinez, Daniel Z Bar, Leonardo D'Aiuto, Or A Shemesh","doi":"10.1016/j.celrep.2024.115109","DOIUrl":"10.1016/j.celrep.2024.115109","url":null,"abstract":"Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples. Expression of the herpesvirus protein ICP27 increases with AD severity and strongly colocalizes with p-tau but not with Aβ. Modeling in human brain organoids shows that HSV-1 infection elevates tau phosphorylation. Notably, p-tau reduces ICP27 expression and markedly decreases post-infection neuronal death from 64% to 7%. This modeling prompts investigation into the cGAS-STING-TBK1 pathway products, nuclear factor (NF)-κB and IRF-3, which colocalizes with ICP27 and p-tau in AD. Furthermore, experimental activation of STING enhances tau phosphorylation, while TBK1 inhibition prevents it. Together, these findings suggest that tau phosphorylation acts as an innate immune response in AD, driven by cGAS-STING.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115109"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926818","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 glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila. 胶质udp -糖基转移酶Ugt35b通过维持果蝇脂质稳态来调节寿命。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2024-12-24 DOI: 10.1016/j.celrep.2024.115099

Lihong Sheng, Jianpeng Gao, Qingyuan Wei, Ye Gong, Zhi-Xiang Xu

引用次数: 0

Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis. cd101阴性中性粒细胞在I型干扰素介导的结核病免疫发病机制中的致病作用。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2024-12-17 DOI: 10.1016/j.celrep.2024.115072

Mohd Saqib, Shreya Das, Tanvir N Nafiz, Elizabeth McDonough, Poornima Sankar, Lokesh K Mishra, Ximeng Zhang, Yi Cai, Selvakumar Subbian, Bibhuti B Mishra

{"title":"Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis.","authors":"Mohd Saqib, Shreya Das, Tanvir N Nafiz, Elizabeth McDonough, Poornima Sankar, Lokesh K Mishra, Ximeng Zhang, Yi Cai, Selvakumar Subbian, Bibhuti B Mishra","doi":"10.1016/j.celrep.2024.115072","DOIUrl":"10.1016/j.celrep.2024.115072","url":null,"abstract":"Neutrophils are vital for immunity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), yet their heterogeneous nature suggests a complex role in TB pathogenesis. Here, we identify two distinct neutrophil populations based on CD101 expression, highlighting their divergent roles in TB. CD101-negative (CD101-ve) neutrophils, which resemble immature, pro-inflammatory granulocytes, exhibit reduced Mtb phagocytosis compared to their mature, CD101-positive (CD101+ve) counterparts. Our findings reveal that type I interferons (IFN-Is) suppress neutrophil Mtb uptake and drive the recruitment of CD101-ve neutrophils to the lungs. Infiltration of these cells promotes Mtb extracellular persistence, exacerbates epithelial damage, and impairs surfactant production. Furthermore, we demonstrate that granulocyte colony-stimulating factor (G-CSF) and chemokine receptor CXCR2 are essential for the pulmonary accumulation of CD101-ve neutrophils. Our study uncovers a pathogenic role for CD101-ve neutrophils in TB and highlights the IFN-I-dependent recruitment of this functionally compromised immature neutrophil as a driver of TB immunopathogenesis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115072"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853146","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

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa. 代谢转录组学指示视锥光感受器对视网膜色素变性的反应。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2024-12-21 DOI: 10.1016/j.celrep.2024.115160

Sang Joon Lee, Douglas Emery, Eric Vukmanic, Yekai Wang, Xiaoqin Lu, Wei Wang, Enzo Fortuny, Robert James, Henry J Kaplan, Yongqing Liu, Jianhai Du, Douglas C Dean

引用次数: 0

SLC7A5 is required for cancer cell growth under arginine-limited conditions. SLC7A5是癌细胞在精氨酸限制条件下生长所必需的。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-03 DOI: 10.1016/j.celrep.2024.115130

Kyle N Dunlap, Austin Bender, Alexis Bowles, Alex J Bott, Joshua Tay, Allie H Grossmann, Jared Rutter, Gregory S Ducker

{"title":"SLC7A5 is required for cancer cell growth under arginine-limited conditions.","authors":"Kyle N Dunlap, Austin Bender, Alexis Bowles, Alex J Bott, Joshua Tay, Allie H Grossmann, Jared Rutter, Gregory S Ducker","doi":"10.1016/j.celrep.2024.115130","DOIUrl":"10.1016/j.celrep.2024.115130","url":null,"abstract":"Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter. Using isotope tracing experiments, we show that citrulline uptake and metabolism into arginine are dependent upon expression of SLC7A5. Pharmacological inhibition of SLC7A5 blocks growth under low-arginine conditions across a diverse group of cancer cell lines. Loss of SLC7A5 reduces tumor growth and citrulline import in a mouse tumor model. We identify a conditionally essential role for SLC7A5 in arginine metabolism, and we propose that SLC7A5-targeting therapeutic strategies in cancer may be effective in the context of arginine limitation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115130"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930800","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

IL-21 shapes the B cell response in a context-dependent manner. IL-21以上下文依赖的方式塑造B细胞反应。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-09 DOI: 10.1016/j.celrep.2024.115190

Youngjun Kim, Francesca Manara, Simon Grassmann, Kalina T Belcheva, Kanelly Reyes, Hyunu Kim, Stephanie Downs-Canner, William T Yewdell, Joseph C Sun, Jayanta Chaudhuri

引用次数: 0

Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors. 病毒传感器和限制因子的解剖、亚群和hiv依赖性表达。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-10 DOI: 10.1016/j.celrep.2024.115202

Ashley F George, Jason Neidleman, Xiaoyu Luo, Julie Frouard, Natalie Elphick, Kailin Yin, Kyrlia C Young, Tongcui Ma, Alicer K Andrew, Ifeanyi J Ezeonwumelu, Jesper G Pedersen, Antoine Chaillon, Magali Porrachia, Brendon Woodworth, Martin R Jakobsen, Reuben Thomas, Davey M Smith, Sara Gianella, Nadia R Roan

{"title":"Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.","authors":"Ashley F George, Jason Neidleman, Xiaoyu Luo, Julie Frouard, Natalie Elphick, Kailin Yin, Kyrlia C Young, Tongcui Ma, Alicer K Andrew, Ifeanyi J Ezeonwumelu, Jesper G Pedersen, Antoine Chaillon, Magali Porrachia, Brendon Woodworth, Martin R Jakobsen, Reuben Thomas, Davey M Smith, Sara Gianella, Nadia R Roan","doi":"10.1016/j.celrep.2024.115202","DOIUrl":"10.1016/j.celrep.2024.115202","url":null,"abstract":"We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4+ T cells are not. In lymph node CD4+ Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency. We also identify small subsets of bone marrow-, lung-, and gut-associated CD4+ T and myeloid cells expressing high levels of restriction factors targeting most stages of the HIV replication cycle. In vitro, HIV preferentially fuses to CD4+ T cells with a permissive VISOR profile, but early induction of select VISORs by T1IFN prevents productive HIV infection. Our findings document the diverse patterns of VISOR profiles across tissues and cellular subsets and define their association with susceptibility to HIV.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115202"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969708","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

Tumor-induced metabolic immunosuppression: Mechanisms and therapeutic targets. 肿瘤诱导的代谢免疫抑制：机制和治疗靶点。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-10 DOI: 10.1016/j.celrep.2024.115206

Jean-Ehrland Ricci

引用次数: 0

Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex. 协调的神经元特异性剪接事件限制了LSD1组蛋白去甲基化酶复合物的核小体参与。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-15 DOI: 10.1016/j.celrep.2024.115213

Robert S Porter, Sojin An, Maria C Gavilan, Masayoshi Nagai, Yumie Murata-Nakamura, Bo Zhou, Katherine M Bonefas, Olivier Dionne, Jeru Manoj Manuel, Joannie St-Germain, Suzanne Gascon, Jacqueline Kim, Liam Browning, Benoit Laurent, Uhn-Soo Cho, Shigeki Iwase

{"title":"Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.","authors":"Robert S Porter, Sojin An, Maria C Gavilan, Masayoshi Nagai, Yumie Murata-Nakamura, Bo Zhou, Katherine M Bonefas, Olivier Dionne, Jeru Manoj Manuel, Joannie St-Germain, Suzanne Gascon, Jacqueline Kim, Liam Browning, Benoit Laurent, Uhn-Soo Cho, Shigeki Iwase","doi":"10.1016/j.celrep.2024.115213","DOIUrl":"10.1016/j.celrep.2024.115213","url":null,"abstract":"Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A. We found that neuronal LSD1 splicing reduces the enzymes' affinity to the nucleosome. Meanwhile, neuronal PHF21A splicing significantly attenuates histone H3 binding and further ablates the DNA-binding function exerted by an AT-hook motif. Furthermore, in vitro reconstitution of the canonical and neuronal PHF21A-LSD1 complexes, combined with in vivo methylation mapping, identified the neuronal complex as a hypomorphic H3K4 demethylating machinery. The neuronal PHF21A, albeit with its weaker nucleosome binding, is necessary for normal gene expression and the H3K4 landscape in the developing brain. Thus, ubiquitously expressed chromatin regulatory complexes can exert neuron-specific functions via alternative splicing of their subunits.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115213"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000708","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

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy. p38α介导的磷酸化和prmt1介导的精氨酸甲基化在驱动TDP-43蛋白病变中的相反作用。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-14 DOI: 10.1016/j.celrep.2024.115205

Mari Aikio, Hana M Odeh, Heike J Wobst, Bo Lim Lee, Úna Chan, Jocelyn C Mauna, Korrie L Mack, Bradley Class, Thomas A Ollerhead, Alice F Ford, Edward M Barbieri, Ryan R Cupo, Lauren E Drake, Joshua L Smalley, Yuan-Ta Lin, Stephanie Lam, Reuben Thomas, Nicholas Castello, Ashmita Baral, Jenna N Beyer, Mohd A Najar, John Dunlop, Aaron D Gitler, Ashkan Javaherian, Julia A Kaye, George M Burslem, Dean G Brown, Christopher J Donnelly, Steven Finkbeiner, Stephen J Moss, Nicholas J Brandon, James Shorter

{"title":"Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.","authors":"Mari Aikio, Hana M Odeh, Heike J Wobst, Bo Lim Lee, Úna Chan, Jocelyn C Mauna, Korrie L Mack, Bradley Class, Thomas A Ollerhead, Alice F Ford, Edward M Barbieri, Ryan R Cupo, Lauren E Drake, Joshua L Smalley, Yuan-Ta Lin, Stephanie Lam, Reuben Thomas, Nicholas Castello, Ashmita Baral, Jenna N Beyer, Mohd A Najar, John Dunlop, Aaron D Gitler, Ashkan Javaherian, Julia A Kaye, George M Burslem, Dean G Brown, Christopher J Donnelly, Steven Finkbeiner, Stephen J Moss, Nicholas J Brandon, James Shorter","doi":"10.1016/j.celrep.2024.115205","DOIUrl":"10.1016/j.celrep.2024.115205","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS. However, it is unclear how p38 MAPK affects TDP-43 proteinopathy. Here, we show that p38α MAPK inhibition reduces pathological TDP-43 phosphorylation, aggregation, cytoplasmic mislocalization, and neurotoxicity. Remarkably, p38α MAPK inhibition mitigates aberrant TDP-43 phenotypes in diverse ALS patient-derived motor neurons. p38α MAPK phosphorylates TDP-43 at pathological S409/S410 and S292, which reduces TDP-43 liquid-liquid phase separation (LLPS) but allows pathological TDP-43 aggregation. Moreover, we establish that PRMT1 methylates TDP-43 at R293. Importantly, S292 phosphorylation reduces R293 methylation, and R293 methylation reduces S409/S410 phosphorylation. Notably, R293 methylation permits TDP-43 LLPS and reduces pathological TDP-43 aggregation. Thus, strategies to reduce p38α-mediated TDP-43 phosphorylation and promote PRMT1-mediated R293 methylation could have therapeutic utility for ALS and related TDP-43 proteinopathies.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115205"},"PeriodicalIF":7.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000808","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