Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.
Science
; 377(6606): eabo1984, 2022 08 05.
Article
em En
| MEDLINE
| ID: mdl-35926050
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
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Displasia Arritmogênica Ventricular Direita
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Análise de Célula Única
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Transcriptoma
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Insuficiência Cardíaca
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article