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Amino acid primed mTOR activity is essential for heart regeneration [bulk RNA-seq]

ABSTRACT: Heart disease is the leading cause of death as there is no current method to repair damaged myocardium due to the limited proliferative capacity of adult cardiomyocytes. Curiously, mouse neonates and zebrafish, larvae or adult, are able to regenerate their hearts via cardiomyocyte de-differentiation and proliferation. However, a molecular mechanism of why these cardiomyocytes can re-enter cell cycle is poorly understood. Here, we identify a unique metabolic state that primes adult zebrafish and neonatal mouse ventricular cardiomyocytes to proliferate. Zebrafish and neonatal mouse hearts display elevated glutamine levels, predisposing them to amino acid-driven activation of TOR. We show that this TOR activation is required for zebrafish cardiomyocyte regeneration in vivo. After injury we observe pS6 in both the epicardium and ventricular cardiomyocytes suggesting these are amino acid primed cells necessary for regeneration. Through single cell and system-wide RNA-sequencing, LQC proteomics and microscopy we identify dramatic metabolic and mitochondrial changes during the first week of regeneration. These data suggest that regeneration of zebrafish myocardium is driven by metabolic remodeling and reveals a unique metabolic regulator, TOR-primed state, in which zebrafish and mammalian cardiomyocytes are regeneration competent.

ORGANISM(S): Danio rerio

PROVIDER: GSE188243 | GEO | 2022/01/11

REPOSITORIES: GEO

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Amino acid primed mTOR activity is essential for heart regeneration [scRNA-seq]

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Amino acid priming of mTOR is essential for heart regeneration

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