Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies

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.

Link to article: https://www.science.org/doi/10.1126/science.abo1984

To match Clinical information (supplementary information) with Sample IDs on Zenodo, please access the Excel table "Additional_note_samples.xlsx" on the github repository: https://github.com/heiniglab/DCM_heart_cell_atlas