Cell genomics最新文献_第6页

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

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

Secure and federated quantitative trait loci mapping with privateQTL. 基于privateQTL的安全联合数量性状位点映射。

IF 11.1

Cell genomics Pub Date : 2025-02-12 DOI: 10.1016/j.xgen.2025.100769

Yoolim Annie Choi, Yebin Kim, Peihan Miao, Tuuli Lappalainen, Gamze Gürsoy

引用次数: 0

Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures. 定义癌症中的缺氧：缺氧基因表达特征的里程碑式评估。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-31 DOI: 10.1016/j.xgen.2025.100764

Matteo Di Giovannantonio, Fiona Hartley, Badran Elshenawy, Alessandro Barberis, Dan Hudson, Hana S Shafique, Vincent E S Allott, David A Harris, Simon R Lord, Syed Haider, Adrian L Harris, Francesca M Buffa, Benjamin H L Harris

{"title":"Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.","authors":"Matteo Di Giovannantonio, Fiona Hartley, Badran Elshenawy, Alessandro Barberis, Dan Hudson, Hana S Shafique, Vincent E S Allott, David A Harris, Simon R Lord, Syed Haider, Adrian L Harris, Francesca M Buffa, Benjamin H L Harris","doi":"10.1016/j.xgen.2025.100764","DOIUrl":"10.1016/j.xgen.2025.100764","url":null,"abstract":"Tumor hypoxia drives metabolic shifts, cancer progression, and therapeutic resistance. Challenges in quantifying hypoxia have hindered the exploitation of this potential \"Achilles' heel.\" While gene expression signatures have shown promise as surrogate measures of hypoxia, signature usage is heterogeneous and debated. Here, we present a systematic pan-cancer evaluation of 70 hypoxia signatures and 14 summary scores in 104 cell lines and 5,407 tumor samples using 472 million length-matched random gene signatures. Signature and score choice strongly influenced the prediction of hypoxia in vitro and in vivo. In cell lines, the Tardon signature was highly accurate in both bulk and single-cell data (94% accuracy, interquartile mean). In tumors, the Buffa and Ragnum signatures demonstrated superior performance, with Buffa/mean and Ragnum/interquartile mean emerging as the most promising for prospective clinical trials. This work delivers recommendations for experimental hypoxia detection and patient stratification for hypoxia-targeting therapies, alongside a generalizable framework for signature evaluation.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100764"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076676","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

Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling. 使用单细胞表观遗传和转录组分析定义乳腺癌的调控逻辑。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-02-05 DOI: 10.1016/j.xgen.2025.100765

Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco

{"title":"Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling.","authors":"Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco","doi":"10.1016/j.xgen.2025.100765","DOIUrl":"10.1016/j.xgen.2025.100765","url":null,"abstract":"Annotation of cis-regulatory elements that drive transcriptional dysregulation in cancer cells is critical to understanding tumor biology. Herein, we present matched chromatin accessibility (single-cell assay for transposase-accessible chromatin by sequencing [scATAC-seq]) and transcriptome (single-cell RNA sequencing [scRNA-seq]) profiles at single-cell resolution from human breast tumors and healthy mammary tissues processed immediately following surgical resection. We identify the most likely cell of origin for subtype-specific breast tumors and implement linear mixed-effects modeling to quantify associations between regulatory elements and gene expression in malignant versus normal cells. These data unveil cancer-specific regulatory elements and putative silencer-to-enhancer switching events in cells that lead to the upregulation of clinically relevant oncogenes. In addition, we generate matched scATAC-seq and scRNA-seq profiles for breast cancer cell lines, revealing a conserved oncogenic gene expression program between in vitro and in vivo cells. This work highlights the importance of non-coding regulatory mechanisms that underlie oncogenic processes and the ability of single-cell multi-omics to define the regulatory logic of cancer cells.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100765"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366921","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

Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging. 揭示群体蛋白质组学中的暗物质：与认知和衰老相关的单氨基酸多态性泛分析。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-30 DOI: 10.1016/j.xgen.2025.100763

Xiaojing Gao, Yuanyuan Yin, Yiqian Chen, Ling Lu, Jian Zhao, Xu Lin, Jiarui Wu, Qingrun Li, Rong Zeng

{"title":"Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging.","authors":"Xiaojing Gao, Yuanyuan Yin, Yiqian Chen, Ling Lu, Jian Zhao, Xu Lin, Jiarui Wu, Qingrun Li, Rong Zeng","doi":"10.1016/j.xgen.2025.100763","DOIUrl":"10.1016/j.xgen.2025.100763","url":null,"abstract":"Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such as apolipoprotein E (APOE) in plasma and cerebrospinal fluid at the proteome level. Specifically, the quantification of heterozygous APOE-C112R, including its abundance and ratio, provides insights into the dosage effect and relationship with cognition disorder, which cannot be interpreted at the genomic level. Furthermore, our approach could precisely track age-related changes in APOE-C112R levels. Taken together, this pan-SAP workflow uncovered existing but hidden SAPs in multi-populations, connecting SAP quantification to disease progression and paving the way for broader proteomic investigations in complex diseases.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100763"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076681","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

Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration. 染色体尺度的基因组组装揭示了重复元件如何在蝾螈肢体再生过程中形成非编码RNA景观。

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-27 DOI: 10.1016/j.xgen.2025.100761

Thomas Brown, Ketan Mishra, Ahmed Elewa, Svetlana Iarovenko, Elaiyaraja Subramanian, Alberto Joven Araus, Andreas Petzold, Bastian Fromm, Marc R Friedländer, Lennart Rikk, Miyuki Suzuki, Ken-Ichi T Suzuki, Toshinori Hayashi, Atsushi Toyoda, Catarina R Oliveira, Ekaterina Osipova, Nicholas D Leigh, Maximina H Yun, András Simon

{"title":"Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.","authors":"Thomas Brown, Ketan Mishra, Ahmed Elewa, Svetlana Iarovenko, Elaiyaraja Subramanian, Alberto Joven Araus, Andreas Petzold, Bastian Fromm, Marc R Friedländer, Lennart Rikk, Miyuki Suzuki, Ken-Ichi T Suzuki, Toshinori Hayashi, Atsushi Toyoda, Catarina R Oliveira, Ekaterina Osipova, Nicholas D Leigh, Maximina H Yun, András Simon","doi":"10.1016/j.xgen.2025.100761","DOIUrl":"10.1016/j.xgen.2025.100761","url":null,"abstract":"Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.3 Gb genome of the Iberian ribbed newt, Pleurodeles waltl, with a hitherto unprecedented contiguity and completeness among giant genomes. Utilizing this assembly, we demonstrate conserved synteny as well as genetic rearrangements, such as in the major histocompatibility complex locus. We provide evidence suggesting that intronic repeat elements drive newt-specific circular RNA (circRNA) biogenesis and show their regeneration-specific expression. We also present a comprehensive in-depth annotation and chromosomal mapping of microRNAs, highlighting genomic expansion profiles as well as a distinct regulatory pattern in the regenerating limb. These data reveal links between repeat elements, non-coding RNAs, and adult regeneration and provide key resources for addressing developmental, regenerative, and evolutionary principles.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100761"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061079","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