Pathogenic variants in DCM and ACM genes demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways and differential gene expression.
Observational (n=79)
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.
Reichart et al. (2022) conducted an observational in Dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) (n=79). Pathogenic variants in DCM and ACM genes vs. Control hearts was evaluated on Ventricular cell lineages and transcriptional states. Pathogenic variants in DCM and ACM genes demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways and differential gene expression.