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人类小动脉的染色质相互作用图谱揭示了血压遗传调控的机制。

Chromatin interaction maps of human arterioles reveal mechanisms for the genetic regulation of blood pressure.

作者信息

Liu Yong, Pandey Rajan, Qiu Qiongzi, Liu Pengyuan, Xue Hong, Wang Jingli, Therani Bhavika, Ying Rong, Usa Kristie, Grzybowski Michael, Yang Chun, Mishra Manoj K, Greene Andrew S, Cowley Allen W, Rao Sridhar, Geurts Aron M, Widlansky Michael E, Liang Mingyu

机构信息

Department of Physiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.

Molecular Systems Medicine Initiative, University of Arizona Health Sciences, Tucson, AZ, USA.

出版信息

Nat Commun. 2025 Jul 17;16(1):6577. doi: 10.1038/s41467-025-61656-7.

Abstract

Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is largely absent. Here, we report extensive maps of chromatin interactions, single-cell expression, and other molecular features in human arterioles and uncover mechanisms linking human genetic variants to gene expression in vascular cells and the development of hypertension. Compared to large arteries, arterioles exhibited a higher proportion of pericytes which were enriched for blood pressure (BP)-associated genes. BP-associated single nucleotide polymorphisms (SNPs) were enriched in chromatin interaction regions in arterioles. We linked BP-associated noncoding SNP rs1882961 to gene expression through long-range chromatin contacts and revealed remarkable effects of a 4-bp noncoding genomic segment on hypertension in vivo. We anticipate that our data and findings will advance the study of the numerous diseases involving arterioles.

摘要

微动脉是几乎所有组织中位于毛细血管上游的小血管。尽管微动脉在生理学和疾病中具有广泛而重要的作用,但目前对微动脉功能基因组学的了解却非常有限。在此,我们报告了人类微动脉中染色质相互作用、单细胞表达及其他分子特征的详细图谱,并揭示了将人类遗传变异与血管细胞中的基因表达以及高血压发展相联系的机制。与大动脉相比,微动脉中周细胞的比例更高,且这些周细胞富含与血压(BP)相关的基因。与BP相关的单核苷酸多态性(SNP)在微动脉的染色质相互作用区域中富集。我们通过长程染色质接触将与BP相关的非编码SNP rs1882961与基因表达联系起来,并揭示了一个4碱基对非编码基因组片段在体内对高血压的显著影响。我们预计,我们的数据和发现将推动对涉及微动脉的众多疾病的研究。

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