Plate IV.228 · Publications
Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies
Article in Science, 5 August 2022.
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.
Cite
@article{reichart2022pathogenic,
title = {{Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies}},
author = {Reichart, Daniel and Lindberg, Eric L. and Maatz, Henrike and Miranda, Antonio M. A. and Viveiros, Anissa and Shvetsov, Nikolay and Gärtner, Anna and Nadelmann, Emily R. and Lee, Michael and Kanemaru, Kazumasa and Ruiz-Orera, Jorge and Strohmenger, Viktoria and DeLaughter, Daniel M. and Patone, Giannino and Zhang, Hao and Woehler, Andrew and Lippert, Christoph and Kim, Yuri and Adami, Eleonora and Gorham, Joshua M. and Barnett, Sam N. and Brown, Kemar and Buchan, Rachel J. and Chowdhury, Rasheda A. and Constantinou, Chrystalla and Cranley, James and Felkin, Leanne E. and Fox, Henrik and Ghauri, Ahla and Gummert, Jan and Kanda, Masatoshi and Li, Ruoyan and Mach, Lukas and McDonough, Barbara and Samari, Sara and Shahriaran, Farnoush and Yapp, Clarence and Stanasiuk, Caroline and Theotokis, Pantazis I. and Theis, Fabian J. and van den Bogaerdt, Antoon and Wakimoto, Hiroko and Ware, James S. and Worth, Catherine L. and Barton, Paul J. R. and Lee, Young-Ae and Teichmann, Sarah A. and Milting, Hendrik and Noseda, Michela and Oudit, Gavin Y. and Heinig, Matthias and Seidman, Jonathan G. and Hubner, Norbert and Seidman, Christine E.},
journal = {Science},
publisher = {American Association for the Advancement of Science (AAAS)},
year = {2022},
month = aug,
doi = {10.1126/science.abo1984},
url = {https://doi.org/10.1126/science.abo1984},
pmid = {35926050},
pmcid = {PMC9528698}
}