Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
05 08 2022
05 08 2022
Historique:
entrez:
4
8
2022
pubmed:
5
8
2022
medline:
9
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35926050
doi: 10.1126/science.abo1984
pmc: PMC9528698
mid: NIHMS1835045
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabo1984Subventions
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Organisme : Medical Research Council
ID : MC_UP_1102/20
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL080494
Pays : United States
Organisme : Canadian Institute of Health Research
Organisme : NHLBI NIH HHS
ID : R01 HL084553
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
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