Single-cell transcriptional profiling of hearts during cardiac hypertrophy reveals the role of MAMs in cardiomyocyte subtype switching.
Sci Rep
; 13(1): 8339, 2023 05 23.
Article
em En
| MEDLINE
| ID: mdl-37221368
ABSTRACT
Pathological cardiac hypertrophy is the main predecessor of heart failure. Its pathology is sophisticated, and its progression is associated with multiple cellular processes. To explore new therapeutic approaches, more precise examination of cardiomyocyte subtypes and involved biological processes is required in response to hypertrophic stimuli. Mitochondria and the endoplasmic reticulum (ER) are two crucial organelles associated with the progression of cardiac hypertrophy and are connected through junctions known as mitochondria-associated endoplasmic reticulum membranes (MAMs). Although MAM genes are altered in cardiac hypertrophy, the importance of MAMs in cardiac hypertrophy and the expression pattern of MAMs in certain cardiac cell types require a comprehensive analysis. In this study, we analyzed the temporal expression of MAM proteins in the process of cardiac hypertrophy and observed that MAM-related proteins preferentially accumulated in cardiomyocytes at the initial stage of cardiac hypertrophy and underwent a gradual decline, which was synchronized with the proportion of two cardiomyocyte subtypes (CM2 and CM3). Meanwhile, these subtypes went through a functional switch during cardiac hypertrophy. Trajectory analysis suggested that there was a differentiation trajectory of cardiomyocyte subtypes from high to low MAM protein expression. Distinct regulon modules across different cardiomyocyte cell types were revealed by transcriptional regulatory network analysis. Furthermore, scWGCNA revealed that MAM-related genes were clustered into a module that correlated with diabetic cardiomyopathy. Altogether, we identified cardiomyocyte subtype transformation and the potential critical transcription factors involved, which may serve as therapeutic targets in combating cardiac hypertrophy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
/
Insuficiência Cardíaca
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2023
Tipo de documento:
Article