Cell genomics最新文献

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Unraveling an enhancer-silencer regulatory element showing epistatic interaction with a variant that escaped genome-wide association studies. 揭示一个增强-沉默调控元件,显示与一个逃避全基因组关联研究的变异的上位性相互作用。
IF 11.1
Cell genomics Pub Date : 2025-05-23 DOI: 10.1016/j.xgen.2025.100889
Mathieu Adjemout, Samia Nisar, Amélie Escandell, Romain Torres, Magali Torres, Hong Thu Nguyen Huu, Alassane Thiam, Iris Manosalva, Babacar Mbengue, Alioune Dieye, Véronique Adoue, Salvatore Spicuglia, Pascal Rihet, Sandrine Marquet
{"title":"Unraveling an enhancer-silencer regulatory element showing epistatic interaction with a variant that escaped genome-wide association studies.","authors":"Mathieu Adjemout, Samia Nisar, Amélie Escandell, Romain Torres, Magali Torres, Hong Thu Nguyen Huu, Alassane Thiam, Iris Manosalva, Babacar Mbengue, Alioune Dieye, Véronique Adoue, Salvatore Spicuglia, Pascal Rihet, Sandrine Marquet","doi":"10.1016/j.xgen.2025.100889","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100889","url":null,"abstract":"<p><p>Regulation of gene expression has recently been complicated by identifying Epromoters, a subset of promoters with enhancer function. Here, we uncovered a dual cis-regulatory element, \"ESpromoter,\" exhibiting both enhancer and silencer function as a regulator of the nearby genes ATP2B4 and LAX1 in single human T cells. Through an integrative approach, we pinpointed functional rs11240391, a severe malaria-risk variant that escapes detection in genome-wide association studies, challenging conventional strategies for identifying causal variants. CRISPR-modified cells demonstrated the regulatory effect of ESpromoter and rs11240391 on LAX1 expression and T cell activation. Furthermore, our findings revealed an epistatic interaction between ESpromoter SNPs and rs11240391, impacting severe malaria susceptibility by further reducing LAX1 expression. This groundbreaking discovery challenges the conventional enhancer-silencer dichotomy. It highlights the sophistication of transcriptional regulation and argues for an integrated approach combining genetics, epigenetics, and genomics to identify new therapeutic targets for complex diseases.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100889"},"PeriodicalIF":11.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Early establishment and life course stability of sex biases in the human brain transcriptome. 人类大脑转录组性别偏见的早期建立和生命过程稳定性。
IF 11.1
Cell genomics Pub Date : 2025-05-22 DOI: 10.1016/j.xgen.2025.100890
Clara Benoit-Pilven, Juho V Asteljoki, Jaakko T Leinonen, Juha Karjalainen, Mark J Daly, Taru Tukiainen
{"title":"Early establishment and life course stability of sex biases in the human brain transcriptome.","authors":"Clara Benoit-Pilven, Juho V Asteljoki, Jaakko T Leinonen, Juha Karjalainen, Mark J Daly, Taru Tukiainen","doi":"10.1016/j.xgen.2025.100890","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100890","url":null,"abstract":"<p><p>To elaborate on the origins of the established male-female differences in several brain-related phenotypes, we assessed the patterns of transcriptomic sex biases in the developing and adult human forebrain. We find an abundance of sex differences in expression (sex-DEs) in the prenatal brain, driven by both hormonal and sex-chromosomal factors, and considerable consistency in the sex effects between the developing and adult brain, with little sex-DE exclusive to the adult forebrain. Sex-DE was not enriched in genes associated with brain disorders, consistent with systematic differences in the characteristics of these genes (e.g., constraint). Yet, the genes with persistent sex-DE across the lifespan were overrepresented in disease gene co-regulation networks, pointing to their potential to mediate sex biases in brain phenotypes. Altogether, our work highlights prenatal development as a crucial time point for the establishment of brain sex differences.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100890"},"PeriodicalIF":11.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization. 多种癌症类型骨转移生态系统的单细胞分析揭示了骨定植的趋同和不同机制。
IF 11.1
Cell genomics Pub Date : 2025-05-21 DOI: 10.1016/j.xgen.2025.100888
Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang
{"title":"Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization.","authors":"Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang","doi":"10.1016/j.xgen.2025.100888","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100888","url":null,"abstract":"<p><p>Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs from the same cancer type often fell into different archetypes, while BMs from different cancer types sometimes converged on the same archetype. Additional analyses revealed parallel immunosuppression and bone remodeling mechanisms, some of which were experimentally validated. Overall, we discovered unappreciated heterogeneity of BMs across different cancers.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100888"},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CellWalker2: Multi-omic discovery using hierarchical cell type relationships. CellWalker2:使用分层细胞类型关系的多组学发现。
IF 11.1
Cell genomics Pub Date : 2025-05-20 DOI: 10.1016/j.xgen.2025.100886
Zhirui Hu, Pawel F Przytycki, Katherine S Pollard
{"title":"CellWalker2: Multi-omic discovery using hierarchical cell type relationships.","authors":"Zhirui Hu, Pawel F Przytycki, Katherine S Pollard","doi":"10.1016/j.xgen.2025.100886","DOIUrl":"10.1016/j.xgen.2025.100886","url":null,"abstract":"<p><p>Tissues are composed of cells with a wide range of similarities to each other, yet existing methods for single-cell genomics treat cell types as discrete labels. To address this gap, we developed CellWalker2, a graph diffusion-based model for the annotation and mapping of multi-modal data. With our open-source software package, hierarchically related cell types can be probabilistically matched across contexts and used to annotate cells, genomic regions, or gene sets. Additional features include estimating statistical significance and enabling gene expression and chromatin accessibility to be jointly modeled. Through simulation studies, we show that CellWalker2 performs better than existing methods in cell-type annotation and mapping. We then use multi-omics data from the brain and immune system to demonstrate CellWalker2's ability to assign high-resolution cell-type labels to regulatory elements and TFs and to quantify both conserved and divergent cell-type relationships between species.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100886"},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sequential activation of transcription factors promotes liver regeneration through specific and developmental enhancers. 转录因子的顺序激活通过特异性和发育增强剂促进肝脏再生。
IF 11.1
Cell genomics Pub Date : 2025-05-20 DOI: 10.1016/j.xgen.2025.100887
Palmira Llorens-Giralt, Marina Ruiz-Romero, Ramil Nurtdinov, Macarena Herranz-Itúrbide, Guillermo P Vicent, Florenci Serras, Isabel Fabregat, Montserrat Corominas
{"title":"Sequential activation of transcription factors promotes liver regeneration through specific and developmental enhancers.","authors":"Palmira Llorens-Giralt, Marina Ruiz-Romero, Ramil Nurtdinov, Macarena Herranz-Itúrbide, Guillermo P Vicent, Florenci Serras, Isabel Fabregat, Montserrat Corominas","doi":"10.1016/j.xgen.2025.100887","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100887","url":null,"abstract":"<p><p>The mammalian liver exhibits remarkable regenerative capabilities after injury or resection. Central to this process is the precise modulation of gene expression, driven by changes in chromatin structure and the temporal activation of distal regulatory elements. In this study, we integrated chromatin accessibility and transcriptomic data after partial hepatectomy in mice. We show that the expression of crucial regeneration genes is orchestrated by a diverse array of cis-regulatory elements, including regeneration-specific enhancers and enhancers repurposed from various developmental stages. These enhancers collaborate to activate the transcriptional programs required for hepatocyte priming and proliferation, with their activity initially regulated by the activator protein-1 (AP-1) complex and ATF3, and subsequently by nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) during proliferation. Our results also indicate that hepatic regeneration involves the repression of enhancers regulating liver-specific metabolic functions, particularly those involved in lipid metabolism. This study provides a genome-wide atlas of enhancer-gene interactions, offering new insights into the regulatory mechanisms underlying liver regeneration.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100887"},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating methods for the prediction of cell-type-specific enhancers in the mammalian cortex. 预测哺乳动物皮质细胞类型特异性增强子的评估方法。
IF 11.1
Cell genomics Pub Date : 2025-05-19 DOI: 10.1016/j.xgen.2025.100879
Nelson J Johansen, Niklas Kempynck, Nathan R Zemke, Saroja Somasundaram, Seppe De Winter, Marcus Hooper, Deepanjali Dwivedi, Ruchi Lohia, Fabien Wehbe, Bocheng Li, Darina Abaffyová, Ethan J Armand, Julie De Man, Eren Can Ekşi, Nikolai Hecker, Gert Hulselmans, Vasilis Konstantakos, David Mauduit, John K Mich, Gabriele Partel, Tanya L Daigle, Boaz P Levi, Kai Zhang, Yoshiaki Tanaka, Jesse Gillis, Jonathan T Ting, Yoav Ben-Simon, Jeremy Miller, Joseph R Ecker, Bing Ren, Stein Aerts, Ed S Lein, Bosiljka Tasic, Trygve E Bakken
{"title":"Evaluating methods for the prediction of cell-type-specific enhancers in the mammalian cortex.","authors":"Nelson J Johansen, Niklas Kempynck, Nathan R Zemke, Saroja Somasundaram, Seppe De Winter, Marcus Hooper, Deepanjali Dwivedi, Ruchi Lohia, Fabien Wehbe, Bocheng Li, Darina Abaffyová, Ethan J Armand, Julie De Man, Eren Can Ekşi, Nikolai Hecker, Gert Hulselmans, Vasilis Konstantakos, David Mauduit, John K Mich, Gabriele Partel, Tanya L Daigle, Boaz P Levi, Kai Zhang, Yoshiaki Tanaka, Jesse Gillis, Jonathan T Ting, Yoav Ben-Simon, Jeremy Miller, Joseph R Ecker, Bing Ren, Stein Aerts, Ed S Lein, Bosiljka Tasic, Trygve E Bakken","doi":"10.1016/j.xgen.2025.100879","DOIUrl":"10.1016/j.xgen.2025.100879","url":null,"abstract":"<p><p>Identifying cell-type-specific enhancers is critical for developing genetic tools to study the mammalian brain. We organized the \"Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Cell Type-Specific Enhancers from Cross-Species Multi-Omics\" to evaluate machine learning and feature-based methods for nominating enhancer sequences targeting mouse cortical cell types. Methods were assessed using in vivo data from hundreds of adeno-associated virus (AAV)-packaged, retro-orbitally delivered enhancers. Open chromatin was the strongest predictor of functional enhancers, while sequence models improved prediction of non-functional enhancers and identified cell-type-specific transcription factor codes to inform in silico enhancer design. This challenge establishes a benchmark for enhancer prioritization and highlights computational and molecular features critical for identifying functional cortical enhancers, advancing efforts to map and manipulate gene regulation in the mammalian cortex.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100879"},"PeriodicalIF":11.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phenotypic heterogeneity and plasticity in colorectal cancer metastasis. 结直肠癌转移的表型异质性和可塑性。
IF 11.1
Cell genomics Pub Date : 2025-05-15 DOI: 10.1016/j.xgen.2025.100881
Samuel Ogden, Nasrine Metic, Ozen Leylek, Elise A Smith, Alison M Berner, Ann-Marie Baker, Imran Uddin, Marta Buzzetti, Marco Gerlinger, Trevor Graham, Hemant M Kocher, Mirjana Efremova
{"title":"Phenotypic heterogeneity and plasticity in colorectal cancer metastasis.","authors":"Samuel Ogden, Nasrine Metic, Ozen Leylek, Elise A Smith, Alison M Berner, Ann-Marie Baker, Imran Uddin, Marta Buzzetti, Marco Gerlinger, Trevor Graham, Hemant M Kocher, Mirjana Efremova","doi":"10.1016/j.xgen.2025.100881","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100881","url":null,"abstract":"<p><p>Phenotypic heterogeneity and plasticity in colorectal cancer (CRC) has a crucial role in tumor progression, metastasis, and therapy resistance. However, the regulatory factors and the extrinsic signals driving phenotypic heterogeneity remain unknown. Using a combination of single-cell multiomics and spatial transcriptomics data from primary and metastatic CRC patients, we reveal cancer cell states with regenerative and inflammatory phenotypes that closely resemble metastasis-initiating cells in mouse models. We identify an intermediate population with a hybrid regenerative and stem phenotype. We reveal the transcription factors AP-1 and nuclear factor κB (NF-κB) as their key regulators and show localization of these states in an immunosuppressive niche both at the invasive edge in primary CRC and in liver metastasis. We uncover ligand-receptor interactions predicted to activate the regenerative and inflammatory phenotype in cancer cells. Together, our findings reveal regulatory and signaling factors that mediate distinct cancer cell states and can serve as potential targets to impair metastasis.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100881"},"PeriodicalIF":11.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trans-eQTL hotspots shape complex traits by modulating cellular states. Trans-eQTL热点通过调节细胞状态塑造复杂性状。
IF 11.1
Cell genomics Pub Date : 2025-05-14 Epub Date: 2025-05-05 DOI: 10.1016/j.xgen.2025.100873
Kaushik Renganaath, Frank Wolfgang Albert
{"title":"Trans-eQTL hotspots shape complex traits by modulating cellular states.","authors":"Kaushik Renganaath, Frank Wolfgang Albert","doi":"10.1016/j.xgen.2025.100873","DOIUrl":"10.1016/j.xgen.2025.100873","url":null,"abstract":"<p><p>Regulatory genetic variation shapes gene expression, providing an important mechanism connecting DNA variation and complex traits. The causal relationships between gene expression and complex traits remain poorly understood. Here, we integrated transcriptomes and 46 genetically complex growth traits in a large cross between two strains of the yeast Saccharomyces cerevisiae. We discovered thousands of genetic correlations between gene expression and growth, suggesting potential functional connections. Local regulatory variation was a minor source of these genetic correlations. Instead, genetic correlations tended to arise from multiple independent trans-acting regulatory loci. Trans-acting hotspots that affect the expression of numerous genes accounted for particularly large fractions of genetic growth variation and of genetic correlations between gene expression and growth. Genes with genetic correlations were enriched for similar biological processes across traits but with heterogeneous direction of effect. Our results reveal how trans-acting regulatory hotspots shape complex traits by altering cellular states.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100873"},"PeriodicalIF":11.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integration of biobank-scale genetics and plasma proteomics reveals evidence for causal processes in asthma risk and heterogeneity. 生物库规模遗传学和血浆蛋白质组学的整合揭示了哮喘风险和异质性因果过程的证据。
IF 11.1
Cell genomics Pub Date : 2025-05-14 Epub Date: 2025-04-04 DOI: 10.1016/j.xgen.2025.100840
Lauren J Donoghue, Christian Benner, Diana Chang, Flaviyan Jerome Irudayanathan, Rion K Pendergrass, Brian L Yaspan, Anubha Mahajan, Mark I McCarthy
{"title":"Integration of biobank-scale genetics and plasma proteomics reveals evidence for causal processes in asthma risk and heterogeneity.","authors":"Lauren J Donoghue, Christian Benner, Diana Chang, Flaviyan Jerome Irudayanathan, Rion K Pendergrass, Brian L Yaspan, Anubha Mahajan, Mark I McCarthy","doi":"10.1016/j.xgen.2025.100840","DOIUrl":"10.1016/j.xgen.2025.100840","url":null,"abstract":"<p><p>Hundreds of genetic associations for asthma have been identified, yet translating these findings into mechanistic insights remains challenging. We leveraged plasma proteomics from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify biomarkers and effectors of asthma risk or heterogeneity using genetic causal inference approaches. We identified 609 proteins associated with asthma status (269 proteins after controlling for body mass index [BMI] and smoking). Analysis of genetically predicted protein levels identified 70 proteins with putative causal roles in asthma risk, including known drug targets and proteins without prior genetic evidence in asthma (e.g., GCHFR, TDRKH, and CLEC7A). The genetic architecture of causally associated proteins provided evidence for a Toll-like receptor (TLR)1-interleukin (IL)-27 asthma axis. Lastly, we identified evidence of causal relationships between proteins and heterogeneous aspects of asthma biology, including between TSPAN8 and neutrophil counts. These findings illustrate that integrating biobank-scale genetics and plasma proteomics can provide a framework to identify therapeutic targets and mechanisms underlying disease risk and heterogeneity.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100840"},"PeriodicalIF":11.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ribonuclease activity undermines immune sensing of naked extracellular RNA. 核糖核酸酶活性破坏裸细胞外RNA的免疫感知。
IF 11.1
Cell genomics Pub Date : 2025-05-14 Epub Date: 2025-05-06 DOI: 10.1016/j.xgen.2025.100874
Mauricio Castellano, Valentina Blanco, Marco Li Calzi, Bruno Costa, Kenneth Witwer, Marcelo Hill, Alfonso Cayota, Mercedes Segovia, Juan Pablo Tosar
{"title":"Ribonuclease activity undermines immune sensing of naked extracellular RNA.","authors":"Mauricio Castellano, Valentina Blanco, Marco Li Calzi, Bruno Costa, Kenneth Witwer, Marcelo Hill, Alfonso Cayota, Mercedes Segovia, Juan Pablo Tosar","doi":"10.1016/j.xgen.2025.100874","DOIUrl":"10.1016/j.xgen.2025.100874","url":null,"abstract":"<p><p>Cell membranes are thought of as barriers to extracellular RNA (exRNA) uptake. While naked exRNAs can be spontaneously internalized by certain cells, functional cytosolic delivery has been rarely observed. Here, we show that extracellular ribonucleases (RNases)-primarily from cell culture supplements-have obscured the study of exRNA functionality. When ribonuclease inhibitor (RI) is added to cell cultures, naked exRNAs can trigger pro-inflammatory responses in dendritic cells and macrophages, largely via endosomal Toll-like receptors (TLRs). Moreover, naked exRNAs can escape endosomes, engaging cytosolic RNA sensors. In addition, naked extracellular mRNAs can be spontaneously internalized and translated by various cell types in an RI-dependent manner. In vivo, RI co-injection amplifies naked-RNA-induced activation of splenic lymphocytes and myeloid leukocytes. Furthermore, naked RNA is inherently pro-inflammatory in RNase-poor compartments like the peritoneal cavity. These findings demonstrate that naked RNA is bioactive without requiring vesicular encapsulation, making a case for nonvesicular-exRNA-mediated intercellular communication.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100874"},"PeriodicalIF":11.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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