Science (New York, N.Y.) · 2022

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

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Reichart Daniel, Lindberg Eric L, Maatz Henrike, Miranda Antonio M A, Viveiros Anissa, Shvetsov Nikolay, Gärtner Anna, Nadelmann Emily R, Lee Michael, Kanemaru Kazumasa, Ruiz-Orera Jorge, Strohmenger Viktoria, DeLaughter Daniel M, Patone Giannino, Zhang Hao, Woehler Andrew, Lippert Christoph, Kim Yuri, Adami Eleonora, Gorham Joshua M, Barnett Sam N, Brown Kemar, Buchan Rachel J, Chowdhury Rasheda A, Constantinou Chrystalla, Cranley James, Felkin Leanne E, Fox Henrik, Ghauri Ahla, Gummert Jan, Kanda Masatoshi, Li Ruoyan, Mach Lukas, McDonough Barbara, Samari Sara, Shahriaran Farnoush, Yapp Clarence, Stanasiuk Caroline, Theotokis Pantazis I, Theis Fabian J, van den Bogaerdt Antoon, Wakimoto Hiroko, Ware James S, Worth Catherine L, Barton Paul J R, Lee Young-Ae, Teichmann Sarah A, Milting Hendrik, Noseda Michela, Oudit Gavin Y, Heinig Matthias, Seidman Jonathan G, Hubner Norbert, Seidman Christine E

Аннотация

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.

Предметные рубрики MeSH

Arrhythmogenic Right Ventricular Dysplasia Atlases as Topic Cardiomyopathy, Dilated Cell Nucleus Heart Failure Heart Ventricles Humans RNA-Seq Single-Cell Analysis Transcriptome

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

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Аннотация

Предметные рубрики MeSH