Cell genomics最新文献_第8页

A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans. 在藏族人中，MCUR1附近的高原适应变异降低了其转录并减弱了红细胞生成。

IF 11.1

Cell genomics Pub Date : 2025-03-12 Epub Date: 2025-03-04 DOI: 10.1016/j.xgen.2025.100782

Jie Ping, Xinyi Liu, Yiming Lu, Cheng Quan, Pengcheng Fan, Hao Lu, Qi Li, Cuiling Wang, Zheng Zhang, Mengyu Liu, Shunqi Chen, Lingle Chang, Yuqing Jiang, Qilin Huang, Jie Liu, Tana Wuren, Huifang Liu, Ying Hao, Longli Kang, Guanjun Liu, Hui Lu, Xiaojun Wei, Yuting Wang, Yuanfeng Li, Hao Guo, Yongquan Cui, Haoxiang Zhang, Yang Zhang, Yujia Zhai, Yaoxi He, Wangshan Zheng, Xuebin Qi, Ouzhuluobu, Huiping Ma, Linpeng Yang, Xin Wang, Wanjun Jin, Ying Cui, Rili Ge, Shizheng Wu, Yuan Wei, Bing Su, Fuchu He, Hongxing Zhang, Gangqiao Zhou

{"title":"A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans.","authors":"Jie Ping, Xinyi Liu, Yiming Lu, Cheng Quan, Pengcheng Fan, Hao Lu, Qi Li, Cuiling Wang, Zheng Zhang, Mengyu Liu, Shunqi Chen, Lingle Chang, Yuqing Jiang, Qilin Huang, Jie Liu, Tana Wuren, Huifang Liu, Ying Hao, Longli Kang, Guanjun Liu, Hui Lu, Xiaojun Wei, Yuting Wang, Yuanfeng Li, Hao Guo, Yongquan Cui, Haoxiang Zhang, Yang Zhang, Yujia Zhai, Yaoxi He, Wangshan Zheng, Xuebin Qi, Ouzhuluobu, Huiping Ma, Linpeng Yang, Xin Wang, Wanjun Jin, Ying Cui, Rili Ge, Shizheng Wu, Yuan Wei, Bing Su, Fuchu He, Hongxing Zhang, Gangqiao Zhou","doi":"10.1016/j.xgen.2025.100782","DOIUrl":"10.1016/j.xgen.2025.100782","url":null,"abstract":"To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca2+ uptake and then concomitantly increased cytosolic Ca2+ levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca2+ homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100782"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569170","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

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

Genetic mapping of serum metabolome to chronic diseases among Han Chinese. 汉族慢性疾病血清代谢组遗传定位。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-20 DOI: 10.1016/j.xgen.2024.100743

Chunxiao Cheng, Fengzhe Xu, Xiong-Fei Pan, Cheng Wang, Jiayao Fan, Yunhaonan Yang, Yuanjiao Liu, Lingyun Sun, Xiaojuan Liu, Yue Xu, Yuan Zhou, Congmei Xiao, Wanglong Gou, Zelei Miao, Jiaying Yuan, Luqi Shen, Yuanqing Fu, Xiaohui Sun, Yimin Zhu, Yuming Chen, An Pan, Dan Zhou, Ju-Sheng Zheng

{"title":"Genetic mapping of serum metabolome to chronic diseases among Han Chinese.","authors":"Chunxiao Cheng, Fengzhe Xu, Xiong-Fei Pan, Cheng Wang, Jiayao Fan, Yunhaonan Yang, Yuanjiao Liu, Lingyun Sun, Xiaojuan Liu, Yue Xu, Yuan Zhou, Congmei Xiao, Wanglong Gou, Zelei Miao, Jiaying Yuan, Luqi Shen, Yuanqing Fu, Xiaohui Sun, Yimin Zhu, Yuming Chen, An Pan, Dan Zhou, Ju-Sheng Zheng","doi":"10.1016/j.xgen.2024.100743","DOIUrl":"10.1016/j.xgen.2024.100743","url":null,"abstract":"Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10-11) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100743"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017205","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