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致病变体破坏心肌病的细胞组成和单细胞转录
作者:小柯机器人 发布时间:2022/8/7 19:52:02

美国哈佛医学院Christine E. Seidman等研究人员合作发现,致病变体破坏心肌病的细胞组成和单细胞转录。相关论文发表在2022年8月5日出版的《科学》杂志上。

利用单核RNA测序,研究人员对来自18个对照组和61个有扩张型心肌病(DCM)和心律失常型心肌病(ACM)基因致病变体,或特发性疾病的衰竭的非缺血性人类心脏的88万个核的转录组进行了表征。研究人员对心室细胞谱系和转录状态进行了基因型分层分析。由此产生的DCM和ACM心室细胞图谱显示了不同的右心室和左心室反应,突出了与基因型相关的途径、细胞间的相互作用以及单细胞分辨率下的不同基因表达。这些数据共同阐明了人类心力衰竭的共同和不同的细胞和分子结构,并提出了候选治疗靶标。

据悉,导致DCM和ACM的基因中的致病变体通过未知的机制传达了心衰发展的高风险。

附:英文原文

Title: Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies

Author: Daniel Reichart, Eric L. Lindberg, Henrike Maatz, Antonio M. A. Miranda, Anissa Viveiros, Nikolay Shvetsov, Anna Grtner, Emily R. Nadelmann, Michael Lee, Kazumasa Kanemaru, Jorge Ruiz-Orera, Viktoria Strohmenger, Daniel M. DeLaughter, Giannino Patone, Hao Zhang, Andrew Woehler, Christoph Lippert, Yuri Kim, Eleonora Adami, Joshua M. Gorham, Sam N. Barnett, Kemar Brown, Rachel J. Buchan, Rasheda A. Chowdhury, Chrystalla Constantinou, James Cranley, Leanne E. Felkin, Henrik Fox, Ahla Ghauri, Jan Gummert, Masatoshi Kanda, Ruoyan Li, Lukas Mach, Barbara McDonough, Sara Samari, Farnoush Shahriaran, Clarence Yapp, Caroline Stanasiuk, Pantazis I. Theotokis, Fabian J. Theis, Antoon van den Bogaerdt, Hiroko Wakimoto, James S. Ware, Catherine L. Worth, Paul J. R. Barton, Young-Ae Lee, Sarah A. Teichmann, Hendrik Milting, Michela Noseda, Gavin Y. Oudit, Matthias Heinig, Jonathan G. Seidman, Norbert Hubner, Christine E. Seidman

Issue&Volume: 2022-08-05

Abstract: Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.

DOI: abo1984

Source: https://www.science.org/doi/10.1126/science.abo1984

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037