Pathogenic variants damage cell composition and single-cell transcription in cardiomyopathies

Reichart D, Lindberg EL, Maatz H, Miranda AMA, Viveiros A, Shvetsov N, Gaertner A, Nadelmann ER, Lee M, Kanemaru K, Ruiz-Orera J, Strohmenger V, Delaughter DM, Patone G, Zhang H, Woehler A, Lippert C, Kim Y, Adami E, Gorham JM, Barnett SN, Brown K, Buchan RJ, Chowdhury RA, Constantinou C, Cranley J, Felkin LE, Fox H, Ghauri A, Gummert J, Kanda M, Li R, Mach L, Mcdonough B, Samari S, Shahriaran F, Yapp C, Stanasiuk C, Theotokis P, Theis FJ, Van Den Bogaerdt A, Wakimoto H, Ware JS, Worth CL, Barton PJR, Lee YA, Teichmann SA, Milting H, Noseda M, Oudit GY, Heinig M, Seidman JG, Hubner N, Seidman CE (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Science American Association for the Advancement of Science

Book Volume: 377

Article Number: abo1984

Journal Issue: 6606

DOI: 10.1126/science.abo1984

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.

Involved external institutions

Harvard University US United States (USA) (US) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) University of Alberta CA Canada (CA) Ruhr-Universität Bochum (RUB) DE Germany (DE) Genome Research Limited GB United Kingdom (GB) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) ETB-BISLIFE NL Netherlands (NL) Universität Potsdam DE Germany (DE) Brigham and Women's Hospital (BWH) US United States (USA) (US)

How to cite

APA:

Reichart, D., Lindberg, E.L., Maatz, H., Miranda, A.M.A., Viveiros, A., Shvetsov, N.,... Seidman, C.E. (2022). Pathogenic variants damage cell composition and single-cell transcription in cardiomyopathies. Science, 377(6606). https://doi.org/10.1126/science.abo1984

MLA:

Reichart, Daniel, et al. "Pathogenic variants damage cell composition and single-cell transcription in cardiomyopathies." Science 377.6606 (2022).

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