Cell genomics最新文献_第7页

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

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

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

An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. 一种古老的ACSF3调节变异通过代谢稳态影响人类身高和基础代谢率的共同进化。

IF 11.1

Cell genomics Pub Date : 2025-06-11 Epub Date: 2025-05-21 DOI: 10.1016/j.xgen.2025.100855

Yufeng Zhang, Jie Wang, Chuanyou Yi, Yue Su, Zi Yin, Shuxian Zhang, Li Jin, Mark Stoneking, Jian Yang, Ke Wang, He Huang, Jin Li, Shaohua Fan

{"title":"An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis.","authors":"Yufeng Zhang, Jie Wang, Chuanyou Yi, Yue Su, Zi Yin, Shuxian Zhang, Li Jin, Mark Stoneking, Jian Yang, Ke Wang, He Huang, Jin Li, Shaohua Fan","doi":"10.1016/j.xgen.2025.100855","DOIUrl":"10.1016/j.xgen.2025.100855","url":null,"abstract":"Anatomically modern humans (AMHs) exhibit a significant increase in basal metabolic rate (BMR) and height compared to non-human apes. This study investigates the genetic basis underlying these traits. Our analyses reveal a strong genetic correlation between height and BMR. A regulatory mutation, rs34590044-A, was found to be associated with the increased height and BMR in AMHs. rs34590044-A upregulates the expression of ACSF3 by increasing its enhancer activity, leading to increased body length and BMR in mice fed essential amino acids which are characteristic of meat-based diets. In the British population, rs34590044-A has been under positive selection over the past 20,000 years, with a particularly strong signal in the last 5,000 years, as also evidenced by ancient DNA analysis. These results suggest that the emergence of rs34590044-A may have facilitated the adaptation to a meat-enriched diet in AMHs, with increased height and BMR as consequences of this dietary shift.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100855"},"PeriodicalIF":11.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129591","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

ESC models of autism with copy-number variations reveal cell-type-specific translational vulnerability. 具有拷贝数变异的自闭症ESC模型揭示了细胞类型特异性的翻译脆弱性。

IF 11.1

Cell genomics Pub Date : 2025-06-11 DOI: 10.1016/j.xgen.2025.100877

Jun Nomura, Amila Zuko, Keiko Kishimoto, Hiroaki Mutsumine, Hiroko Maegawa, Kazumi Fukatsu, Yoshiko Nomura, Xiaoxi Liu, Nobuhiro Nakai, Eiki Takahashi, Tsukasa Kouno, Jay W Shin, Toru Takumi

{"title":"ESC models of autism with copy-number variations reveal cell-type-specific translational vulnerability.","authors":"Jun Nomura, Amila Zuko, Keiko Kishimoto, Hiroaki Mutsumine, Hiroko Maegawa, Kazumi Fukatsu, Yoshiko Nomura, Xiaoxi Liu, Nobuhiro Nakai, Eiki Takahashi, Tsukasa Kouno, Jay W Shin, Toru Takumi","doi":"10.1016/j.xgen.2025.100877","DOIUrl":"10.1016/j.xgen.2025.100877","url":null,"abstract":"Human genetics has identified numerous copy-number variations (CNVs) associated with autism spectrum disorders (ASDs). However, the lack of standardized biological resources impedes understanding of the cell-type-specific common features of ASD. Here, we establish a biological resource including 63 genetically modified mouse embryonic stem cell (ESC) lines as genetic models of ASD. We perform neural differentiation using 12 representative cell lines, and their comprehensive analyses, including single-cell RNA sequencing, uncover cell-type-specific susceptible pathways. Moreover, we find that a common phenotype in glutamatergic and GABAergic neurons is reduced expression of Upf3b, a core member of the translational termination and nonsense-mediated decay (NMD). This finding emphasizes that the dysfunction of translational machinery in the developing neurons can be a possible target of early intervention for ASD. This ESC model bank becomes an invaluable resource for studies in vitro and in vivo of ASD or other neuropsychiatric disorders.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 6","pages":"100877"},"PeriodicalIF":11.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287412","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

Nanopore direct RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between regulatory features. 人类转录组的纳米孔直接RNA测序揭示了mRNA修饰的复杂性和调控特征之间的串扰。

IF 11.1

Cell genomics Pub Date : 2025-06-11 Epub Date: 2025-05-12 DOI: 10.1016/j.xgen.2025.100872

Yerin Kim, Luke Saville, Kieran O'Neill, Jean-Michel Garant, Yilin Liu, Simon Haile-Merhu, Maryam Ghashghaei, Quang Anh Hoang, Amber Louwagie, Yongjin P Park, Steven J M Jones, Ly P Vu

{"title":"Nanopore direct RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between regulatory features.","authors":"Yerin Kim, Luke Saville, Kieran O'Neill, Jean-Michel Garant, Yilin Liu, Simon Haile-Merhu, Maryam Ghashghaei, Quang Anh Hoang, Amber Louwagie, Yongjin P Park, Steven J M Jones, Ly P Vu","doi":"10.1016/j.xgen.2025.100872","DOIUrl":"10.1016/j.xgen.2025.100872","url":null,"abstract":"The identification and functional characterization of chemical modifications on an mRNA molecule, in particular N6-methyladenosine (m6A) modification, significantly broadened our understanding of RNA function and regulation. While interactions between RNA modifications and other RNA features have been proposed, direct evidence showing correlation is limited. Here, using Oxford Nanopore long-read direct RNA sequencing (dRNA-seq), we simultaneously interrogate the transcriptome and epitranscriptome of a human leukemia cell line to investigate the correlation between m6A modifications, mRNA abundance, mRNA stability, polyadenylation (poly(A)) tail length, and alternative splicing. High-quality dRNA-seq is important for unbiased and large-scale correlative analyses. Global assessments indicated a negative association between poly(A) tail length and mRNA abundance while uncovering pathway-specific responses upon depletion of the m6A-forming enzyme METTL3. Overall, our study presented a rich dRNA-seq data resource that has been validated and can be further exploited to inquire into the complexity of RNA modifications and potential interplays between RNA regulatory elements.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100872"},"PeriodicalIF":11.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013530","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