Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies

<p>Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy</p> <p>(ACM) convey high risks for the development of heart failure through unknown mechanisms. Using</p> <p>single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and</p> <p>61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic</p> <p>disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional</p> <p>states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular</p> <p>responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene</p> <p>expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and</p> <p>molecular architectures of human heart failure and suggest candidate therapeutic targets.</p> <p>&nbsp;</p> <p>Link to article: https://www.science.org/doi/10.1126/science.abo1984</p> <p>To match Clinical information (supplementary information) with Sample IDs on Zenodo, please access the Excel table &quot;Additional_note_samples.xlsx&quot; on the github repository:&nbsp;https://github.com/heiniglab/DCM_heart_cell_atlas</p>