| Literature DB >> 35926050 |
Daniel Reichart1,2,3, Eric L Lindberg4, Henrike Maatz4,5, Hendrik Milting6, Michela Noseda7,8, Gavin Y Oudit9,10, Matthias Heinig11,12,13, Jonathan G Seidman1, Norbert Hubner4,5,14, Christine E Seidman1,2,15, Antonio M A Miranda7,8, Anissa Viveiros9,10, Nikolay Shvetsov4, Anna Gärtner6, Emily R Nadelmann1, Michael Lee7, Kazumasa Kanemaru16, Jorge Ruiz-Orera4, Viktoria Strohmenger1,17, Daniel M DeLaughter1,15, Giannino Patone4, Hao Zhang9,10, Andrew Woehler18, Christoph Lippert19,20, Yuri Kim1,2, Eleonora Adami4, Joshua M Gorham1, Sam N Barnett7, Kemar Brown1,21, Rachel J Buchan7,22, Rasheda A Chowdhury7, Chrystalla Constantinou7, James Cranley16, Leanne E Felkin7,22, Henrik Fox23, Ahla Ghauri24, Jan Gummert23, Masatoshi Kanda4,25, Ruoyan Li16, Lukas Mach7,22, Barbara McDonough2,15, Sara Samari7, Farnoush Shahriaran11, Clarence Yapp26, Caroline Stanasiuk6, Pantazis I Theotokis7,27, Fabian J Theis11, Antoon van den Bogaerdt28, Hiroko Wakimoto1, James S Ware7,22,27, Catherine L Worth4, Paul J R Barton7,22,27, Young-Ae Lee24,29, Sarah A Teichmann16,30.
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.Entities:
Mesh：
Year: 2022 PMID： 35926050 PMCID： PMC9528698 DOI： 10.1126/science.abo1984
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714