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.

中文翻译：

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致病变异破坏心肌病中的细胞组成和单细胞转录

导致扩张型心肌病 (DCM) 和致心律失常性心肌病 (ACM) 的基因的致病变异通过未知机制传递了发生心力衰竭的高风险。使用单核 RNA 测序，我们对来自 18 个对照和 61 个衰竭的非缺血性人类心脏的 880,000 个细胞核的转录组进行了表征，这些心脏具有 DCM 和 ACM 基因的致病变异或特发性疾病。我们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 心室细胞图谱显示出明显的右心室和左心室反应，突出了基因型相关通路、细胞间相互作用和单细胞分辨率下的差异基因表达。一起，