Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging
Protein & Cell
; (12): 279-293, 2023.
Article
en En
| WPRIM
| ID: wpr-982546
Biblioteca responsable:
WPRO
ABSTRACT
Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
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Texto completo:
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Índice:
WPRIM
Asunto principal:
Primates
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Proteínas Represoras
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Envejecimiento
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Miocitos Cardíacos
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Factores de Transcripción Forkhead
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Transcriptoma
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Macaca fascicularis
Límite:
Animals
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Humans
Idioma:
En
Revista:
Protein & Cell
Año:
2023
Tipo del documento:
Article