Cell genomics最新文献_第2页

SpaLinker identifies phenotype-associated spatial tumor microenvironment features by integrating bulk and spatial sequencing data. SpaLinker通过整合大量和空间测序数据来识别与表型相关的空间肿瘤微环境特征。

IF 11.1

Cell genomics Pub Date : 2025-07-09 Epub Date: 2025-06-05 DOI: 10.1016/j.xgen.2025.100893

Xiaojie Cheng, Chen Tang, Kejing Dong, Yuzhou You, Xueying Zhao, Bin Duan, Shaoqi Chen, Guohui Chuai, Zhenbo Zhang, Qi Liu

{"title":"SpaLinker identifies phenotype-associated spatial tumor microenvironment features by integrating bulk and spatial sequencing data.","authors":"Xiaojie Cheng, Chen Tang, Kejing Dong, Yuzhou You, Xueying Zhao, Bin Duan, Shaoqi Chen, Guohui Chuai, Zhenbo Zhang, Qi Liu","doi":"10.1016/j.xgen.2025.100893","DOIUrl":"10.1016/j.xgen.2025.100893","url":null,"abstract":"The emergence of spatial transcriptomics (ST) technology offers unprecedented opportunities to elucidate the complexity and heterogeneity of the tumor microenvironment (TME). However, quantitatively linking spatially resolved features with clinical phenotypes remains challenging due to the scarcity of clinical annotations of spatial sequencing samples. Herein, we introduce SpaLinker, an innovative integrated framework that utilizes ST data to decipher spatially resolved TMEs at molecular, cellular, and tissue structure levels. Specifically, it assesses the prognostic significance of spatially defined features by integrating well-accumulated bulk RNA sequencing (RNA-seq) data, using a phenotype-driven computational framework. Applying SpaLinker to diverse tumor ST datasets demonstrated its utility and effectiveness in recognizing spatial architectures, including tertiary lymphoid structures and tumor-normal interfaces, and in establishing links to distinct clinical outcomes. Overall, this study presents a valuable and comprehensive pan-cancer analytical platform to de novo identify phenotype-associated spatial TME features, significantly enhancing the clinical utility of spatial sequencing technology.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100893"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peripheral chromatin remodeling at the center of zygotic genome activation. 外周染色质重塑在合子基因组激活的中心。

IF 11.1

Cell genomics Pub Date : 2025-07-09 DOI: 10.1016/j.xgen.2025.100922

Laure de Chancel, Jean-Léon Maître

引用次数: 0

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity. 细胞外囊泡转录组提供了与肥胖疾病易感性相关的组织特异性功能基因组注释。

IF 11.1

Cell genomics Pub Date : 2025-07-09 DOI: 10.1016/j.xgen.2025.100925

Emeli Chatterjee, Michael J Betti, Quanhu Sheng, Phillip Lin, Margo P Emont, Guoping Li, Kaushik Amancherla, Marta Garcia-Contreras, Priyanka Gokulnath, Worawan B Limpitikul, Olivia Rosina Whittaker, Kathy Luong, Christopher Azzam, Denise Gee, Matthew Hutter, Karen Flanders, Parul Sahu, Charles R Flynn, Jonathan Brown, Danxia Yu, Evan D Rosen, Kendall Van-Keuren Jensen, Eric R Gamazon, Ravi Shah, Saumya Das

{"title":"The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.","authors":"Emeli Chatterjee, Michael J Betti, Quanhu Sheng, Phillip Lin, Margo P Emont, Guoping Li, Kaushik Amancherla, Marta Garcia-Contreras, Priyanka Gokulnath, Worawan B Limpitikul, Olivia Rosina Whittaker, Kathy Luong, Christopher Azzam, Denise Gee, Matthew Hutter, Karen Flanders, Parul Sahu, Charles R Flynn, Jonathan Brown, Danxia Yu, Evan D Rosen, Kendall Van-Keuren Jensen, Eric R Gamazon, Ravi Shah, Saumya Das","doi":"10.1016/j.xgen.2025.100925","DOIUrl":"10.1016/j.xgen.2025.100925","url":null,"abstract":"We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 × 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100925"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651382","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

Stop codon context modulates NMD efficiency through translation termination kinetics. 终止密码子上下文通过翻译终止动力学调节NMD效率。

IF 11.1

Cell genomics Pub Date : 2025-07-09 DOI: 10.1016/j.xgen.2025.100948

Dasa Longman, Laura Monaghan, Javier F Cáceres

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 : 2025-07-09 Epub Date: 2025-05-19 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":"10.1016/j.xgen.2025.100881","url":null,"abstract":"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.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100881"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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 : 2025-07-09 Epub Date: 2025-05-23 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":"10.1016/j.xgen.2025.100888","url":null,"abstract":"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.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100888"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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 : 2025-07-09 Epub Date: 2025-05-22 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":"10.1016/j.xgen.2025.100887","url":null,"abstract":"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.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100887"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-07-09 Epub Date: 2025-05-28 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":"10.1016/j.xgen.2025.100889","url":null,"abstract":"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.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100889"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OmicsTweezer: A distribution-independent cell deconvolution model for multi-omics Data. OmicsTweezer：多组学数据的分布无关细胞反卷积模型。

IF 11.1

Cell genomics Pub Date : 2025-07-08 DOI: 10.1016/j.xgen.2025.100950

Xinxing Yang, Faming Zhao, Tao Ren, Canping Chen, Katelyn T Byrne, Alexey V Danilov, Rosalie C Sears, Peter S Nelson, Lisa M Coussens, Gordon B Mills, Zheng Xia

{"title":"OmicsTweezer: A distribution-independent cell deconvolution model for multi-omics Data.","authors":"Xinxing Yang, Faming Zhao, Tao Ren, Canping Chen, Katelyn T Byrne, Alexey V Danilov, Rosalie C Sears, Peter S Nelson, Lisa M Coussens, Gordon B Mills, Zheng Xia","doi":"10.1016/j.xgen.2025.100950","DOIUrl":"10.1016/j.xgen.2025.100950","url":null,"abstract":"Cell deconvolution estimates cell type proportions from bulk omics data, enabling insights into tissue microenvironments and disease. However, practical applications are often hindered by batch effects between bulk data and referenced single-cell data, a challenge that is frequently overlooked. To address this discrepancy, we developed OmicsTweezer, a distribution-independent cell deconvolution model. By integrating optimal transport with deep learning, OmicsTweezer aligns simulated and real data in a shared latent space, effectively mitigating data shifts and inter-omics distribution differences. OmicsTweezer is versatile, capable of deconvolving bulk RNA-seq, bulk proteomics, and spatial transcriptomics. Extensive evaluations on simulated and real-world datasets demonstrate its robustness and accuracy. Furthermore, applications in prostate and colon cancer showcase OmicsTweezer's ability to identify biologically meaningful cell types. As a unified deconvolution framework for multi-omics data, OmicsTweezer offers an efficient and powerful tool for studying disease microenvironments.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100950"},"PeriodicalIF":11.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661143","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

The CST complex mediates a post-resection non-homologous end joining repair pathway and promotes local deletions in Saccharomyces cerevisiae. CST复合物介导切除后非同源末端连接修复途径，并促进酿酒酵母的局部缺失。

IF 11.1

Cell genomics Pub Date : 2025-07-08 DOI: 10.1016/j.xgen.2025.100947

Oana Ilioaia, Liébaut Dudragne, Clémentine Brocas, Léa Meneu, Romain Koszul, Karine Dubrana, Zhou Xu

{"title":"The CST complex mediates a post-resection non-homologous end joining repair pathway and promotes local deletions in Saccharomyces cerevisiae.","authors":"Oana Ilioaia, Liébaut Dudragne, Clémentine Brocas, Léa Meneu, Romain Koszul, Karine Dubrana, Zhou Xu","doi":"10.1016/j.xgen.2025.100947","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100947","url":null,"abstract":"The repair of a DNA double-strand break (DSB) by non-homologous end joining (NHEJ) generally leaves an intact or minimally modified sequence. Resection exposes single-stranded DNA and directs repair toward homology-dependent pathways and away from NHEJ. Here, we report that in Saccharomyces cerevisiae, the Cdc13/Stn1/Ten1 (CST) complex, characterized for its telomeric functions, acts after resection initiation to mediate a back-up NHEJ repair. We found a CST-specific mutation signature after repair characterized by deletions of 5-85 bp that were mostly dependent on NHEJ, with a subset dependent on microhomology-mediated end joining (MMEJ). The interaction between CST and Polα-primase is critical for these intermediate-size deletions, suggesting a role for fill-in synthesis, thus limiting extensive resection, which would otherwise lead to MMEJ-dependent deletions of several kilobases. Collectively, these results depict a complex picture of repair pathway choice where CST facilitates post-resection NHEJ repair, promoting local deletions but guarding against larger and potentially more deleterious deletions and rearrangements.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100947"},"PeriodicalIF":11.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661144","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