Cell genomics最新文献_第10页

Distance matters: How protein regulators facilitate enhancer-promoter interactions and transcription. 距离问题：蛋白质调节因子如何促进增强子-启动子相互作用和转录。

IF 11.1

Cell genomics Pub Date : 2025-03-12 DOI: 10.1016/j.xgen.2025.100817

Masahiro Nagano, Anders S Hansen

引用次数: 0

Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM. 多组学揭示严重肥胖的关键炎症驱动因素：IL4R， LILRA5和OSM。

IF 11.1

Cell genomics Pub Date : 2025-03-12 Epub Date: 2025-03-04 DOI: 10.1016/j.xgen.2025.100784

Hung-Hsin Chen, Heather M Highland, Elizabeth G Frankel, Alyssa C Scartozzi, Xinruo Zhang, Rashedeh Roshani, Priya Sharma, Asha Kar, Victoria L Buchanan, Hannah G Polikowsky, Lauren E Petty, Jungkyun Seo, Mohammad Yaser Anwar, Daeeun Kim, Mariaelisa Graff, Kristin L Young, Wanying Zhu, Kalypso Karastergiou, Douglas M Shaw, Anne E Justice, Lindsay Fernández-Rhodes, Mohanraj Krishnan, Absalon Gutierrez, Peter J McCormick, Carlos A Aguilar-Salinas, Maria Teresa Tusié-Luna, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Miryoung Lee, Eric R Gamazon, Nancy J Cox, Päivi Pajukanta, Susan K Fried, Penny Gordon-Larsen, Ravi V Shah, Susan P Fisher-Hoch, Joseph B McCormick, Kari E North, Jennifer E Below

{"title":"Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.","authors":"Hung-Hsin Chen, Heather M Highland, Elizabeth G Frankel, Alyssa C Scartozzi, Xinruo Zhang, Rashedeh Roshani, Priya Sharma, Asha Kar, Victoria L Buchanan, Hannah G Polikowsky, Lauren E Petty, Jungkyun Seo, Mohammad Yaser Anwar, Daeeun Kim, Mariaelisa Graff, Kristin L Young, Wanying Zhu, Kalypso Karastergiou, Douglas M Shaw, Anne E Justice, Lindsay Fernández-Rhodes, Mohanraj Krishnan, Absalon Gutierrez, Peter J McCormick, Carlos A Aguilar-Salinas, Maria Teresa Tusié-Luna, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Miryoung Lee, Eric R Gamazon, Nancy J Cox, Päivi Pajukanta, Susan K Fried, Penny Gordon-Larsen, Ravi V Shah, Susan P Fisher-Hoch, Joseph B McCormick, Kari E North, Jennifer E Below","doi":"10.1016/j.xgen.2025.100784","DOIUrl":"10.1016/j.xgen.2025.100784","url":null,"abstract":"Polygenic severe obesity (body mass index [BMI] ≥40 kg/m2) has increased, especially in Hispanic/Latino populations, yet we know little about the underlying mechanistic pathways. We analyzed whole-blood multiomics data to identify genes differentially regulated in severe obesity in Mexican Americans from the Cameron County Hispanic Cohort. Our RNA sequencing analysis identified 124 genes significantly differentially expressed between severe obesity cases (BMI ≥40 kg/m2) and controls (BMI <25 kg/m2); 33% replicated in an independent sample from the same population. Our integrative approach identified inflammatory genes, including IL4R, ZNF438, and LILRA5. Several genes displayed transcriptomic effects on severe obesity in subcutaneous adipose tissue. We further showed that the genetic regulation of these genes is associated with several traits in a large biobank, including bone fractures, obstructive sleep apnea, and hyperaldosteronism, illuminating potential risk mechanisms. Our findings furnish a molecular architecture of the severe obesity phenotype across multiple molecular domains.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100784"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569181","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

Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations. 远程增强子控制基因对调节因子的扰动非常敏感。

IF 11.1

Cell genomics Pub Date : 2025-03-12 Epub Date: 2025-02-25 DOI: 10.1016/j.xgen.2025.100778

Sjoerd J D Tjalsma, Niels J Rinzema, Marjon J A M Verstegen, Michelle J Robers, Andrea Nieto-Aliseda, Richard A Gremmen, Amin Allahyar, Mauro J Muraro, Peter H L Krijger, Wouter de Laat

{"title":"Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations.","authors":"Sjoerd J D Tjalsma, Niels J Rinzema, Marjon J A M Verstegen, Michelle J Robers, Andrea Nieto-Aliseda, Richard A Gremmen, Amin Allahyar, Mauro J Muraro, Peter H L Krijger, Wouter de Laat","doi":"10.1016/j.xgen.2025.100778","DOIUrl":"10.1016/j.xgen.2025.100778","url":null,"abstract":"Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100778"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517561","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

Capturing cell-type-specific activities of cis-regulatory elements from peak-based single-cell ATAC-seq. 从基于峰的单细胞ATAC-seq中捕获顺式调控元件的细胞类型特异性活性。

IF 11.1

Cell genomics Pub Date : 2025-03-12 Epub Date: 2025-03-05 DOI: 10.1016/j.xgen.2025.100806

Mengjie Chen

引用次数: 0

Overcoming collaboration barriers in quantitative trait loci analysis. 克服数量性状位点分析中的协作障碍。

IF 11.1

Cell genomics Pub Date : 2025-02-12 DOI: 10.1016/j.xgen.2025.100773

Wen Zhang, Xiaohong Wu, Jing Gong

引用次数: 0

STMiner: Gene-centric spatial transcriptomics for deciphering tumor tissues. STMiner：以基因为中心的空间转录组学来破译肿瘤组织。

IF 11.1

Cell genomics Pub Date : 2025-02-12 DOI: 10.1016/j.xgen.2025.100771

Peisen Sun, Stephen J Bush, Songbo Wang, Peng Jia, Mingxuan Li, Tun Xu, Pengyu Zhang, Xiaofei Yang, Chengyao Wang, Linfeng Xu, Tingjie Wang, Kai Ye

{"title":"STMiner: Gene-centric spatial transcriptomics for deciphering tumor tissues.","authors":"Peisen Sun, Stephen J Bush, Songbo Wang, Peng Jia, Mingxuan Li, Tun Xu, Pengyu Zhang, Xiaofei Yang, Chengyao Wang, Linfeng Xu, Tingjie Wang, Kai Ye","doi":"10.1016/j.xgen.2025.100771","DOIUrl":"10.1016/j.xgen.2025.100771","url":null,"abstract":"Analyzing spatial transcriptomics data from tumor tissues poses several challenges beyond those of healthy samples, including unclear boundaries between different regions, uneven cell densities, and relatively higher cellular heterogeneity. Collectively, these bias the background against which spatially variable genes are identified, which can result in misidentification of spatial structures and hinder potential insight into complex pathologies. To overcome this problem, STMiner leverages 2D Gaussian mixture models and optimal transport theory to directly characterize the spatial distribution of genes rather than the capture locations of the cells expressing them (spots). By effectively mitigating the impacts of both background bias and data sparsity, STMiner reveals key gene sets and spatial structures overlooked by spot-based analytic tools, facilitating novel biological discoveries. The core concept of directly analyzing overall gene expression patterns also allows for a broader application beyond spatial transcriptomics, positioning STMiner for continuous expansion as spatial omics technologies evolve.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 2","pages":"100771"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416456","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

A multi-modal transformer for cell type-agnostic regulatory predictions. 用于细胞类型不可知的调节预测的多模态变压器。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-29 DOI: 10.1016/j.xgen.2025.100762

Nauman Javed, Thomas Weingarten, Arijit Sehanobish, Adam Roberts, Avinava Dubey, Krzysztof Choromanski, Bradley E Bernstein

引用次数: 0

Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing. 基于crispr的表观基因组编辑激活Prader-Willi综合征基因座。

IF 11.1

Cell genomics Pub Date : 2025-02-12 DOI: 10.1016/j.xgen.2025.100770

Dahlia Rohm, Joshua B Black, Sean R McCutcheon, Alejandro Barrera, Shanté S Berry, Daniel J Morone, Xander Nuttle, Celine E de Esch, Derek J C Tai, Michael E Talkowski, Nahid Iglesias, Charles A Gersbach

{"title":"Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing.","authors":"Dahlia Rohm, Joshua B Black, Sean R McCutcheon, Alejandro Barrera, Shanté S Berry, Daniel J Morone, Xander Nuttle, Celine E de Esch, Derek J C Tai, Michael E Talkowski, Nahid Iglesias, Charles A Gersbach","doi":"10.1016/j.xgen.2025.100770","DOIUrl":"10.1016/j.xgen.2025.100770","url":null,"abstract":"Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi syndrome (PWS) results from loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control the expression of the PWS gene SNRPN from the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternal SNRPN and downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternal SNRPN expression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 2","pages":"100770"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416448","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 DNA sequencing reveals pervasive positive selection throughout preleukemic evolution. 单细胞DNA测序揭示了白血病前期进化过程中普遍存在的正选择。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-21 DOI: 10.1016/j.xgen.2024.100744

Gladys Poon, Aditi Vedi, Mathijs Sanders, Elisa Laurenti, Peter Valk, Jamie R Blundell

引用次数: 0

Single-cell delineation of the microbiota-gut-brain axis: Probiotic intervention in Chd8 haploinsufficient mice. 微生物-肠-脑轴的单细胞描绘：Chd8单倍体不足小鼠的益生菌干预。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-02-05 DOI: 10.1016/j.xgen.2025.100768

Peifeng Ji, Ning Wang, You Yu, Junjie Zhu, Zhenqiang Zuo, Bing Zhang, Fangqing Zhao

{"title":"Single-cell delineation of the microbiota-gut-brain axis: Probiotic intervention in Chd8 haploinsufficient mice.","authors":"Peifeng Ji, Ning Wang, You Yu, Junjie Zhu, Zhenqiang Zuo, Bing Zhang, Fangqing Zhao","doi":"10.1016/j.xgen.2025.100768","DOIUrl":"10.1016/j.xgen.2025.100768","url":null,"abstract":"Emerging research underscores the gut microbiome's impact on the nervous system via the microbiota-gut-brain axis, yet comprehensive insights remain limited. Using a CHD8-haploinsufficient model for autism spectrum disorder (ASD), we explored host-gut microbiota interactions by constructing a single-cell transcriptome atlas of brain and intestinal tissues in wild-type and mutant mice across three developmental stages. CHD8 haploinsufficiency caused delayed development of radial glial precursors and excitatory neural progenitors in the E14.5 brain, inflammation in the adult brain, immunodeficiency, and abnormal intestinal development. Selective CHD8 knockdown in intestinal epithelial cells generated Chd8ΔIEC mice, which exhibited normal sociability but impaired social novelty recognition. Probiotic intervention with Lactobacillus murinus selectively rescued social deficits in Chd8ΔIEC mice, with single-cell transcriptome analysis revealing underlying mechanisms. This study provides a detailed single-cell transcriptomic dataset of ASD-related neural and intestinal changes, advancing our understanding of the gut-brain axis and offering potential therapeutic strategies for ASD.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100768"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366925","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