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Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies

Item Type:Article
Title:Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies
Creators Name:Reichart, D. and Lindberg, E.L. and Maatz, H. and Miranda, A.M.A. and Viveiros, A. and Shvetsov, N. and Gärtner, A. and Nadelmann, E.R. and Lee, M. and Kanemaru, K. and Ruiz-Orera, J. and Strohmenger, V. and DeLaughter, D.M. and Patone, G. and Zhang, H. and Woehler, A. and Lippert, C. and Kim, Y. and Adami, E. and Gorham, J.M. and Barnett, S.N. and Brown, K. and Buchan, R.J. and Chowdhury, R.A. and Constantinou, C. and Cranley, J. and Felkin, L.E. and Fox, H. and Ghauri, A. and Gummert, J. and Kanda, M. and Li, R. and Mach, L. and McDonough, B. and Samari, S. and Shahriaran, F. and Yapp, C. and Stanasiuk, C. and Theotokis, P.I. and Theis, F.J. and van den Bogaerdt, A. and Wakimoto, H. and Ware, J.S. and Worth, C.L. and Barton, P.J.R. and Lee, Y.A. and Teichmann, S.A. and Milting, H. and Noseda, M. and Oudit, G.Y. and Heinig, M. and Seidman, J.G. and Hubner, N. and Seidman, C.E.
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.
Keywords:Cardiomyopathies, Dilated Cardiomyopathy, Heart Failure, Heart Ventricles, Transcriptome
Source:Science
ISSN:0036-8075
Publisher:American Association for the Advancement of Science
Volume:377
Number:6606
Page Range:eabo1984
Date:5 August 2022
Official Publication:https://doi.org/10.1126/science.abo1984
PubMed:View item in PubMed

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