Chromatin landscape in perinatal cardiomyocytes
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE178673 | GEO | 2023/02/03
REPOSITORIES: GEO
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Project description:In this study, we generated nucleotide-resolution translatome as well as transcriptome data of isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORF) were detected from the deep sequencing of ribosome protected fragments orchestrating the shift of translatome in hypertrophied cardiomyocytes.We further identified more than 100 potential micropeptides encoded by uncharacterized small open reading frames (sORFs) in the long noncoding RNA genes. Over two-thirds of these micropeptide candidates were experimentally validated in a random test with three micropeptides showing regulatory function in cardiomyocyte hypertrophy via modulating the activities of Oxidative phosphorylation, Calcium signaling pathway, and MAPK signaling pathway.Our study provided a genome-wide overview of the translational controls of cardiomyocyte hypertrophy and demonstrated an unrecognized role of micropeptides in cardiomyocyte biology.
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2020-08-25 | BIOMD0000000961 | BioModels
Project description:The direct conversion, or trans-differentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provide promising ways of cardiac regeneration. However, genetic manipulations are still not desirable in real clinical applications. we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts with only chemical cocktails. These chemical-induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Microarray-bassed gene expression patterns of Mouse embryonic fibroblasts (MEFs), CiCMs, and cardiomyocytes(CMs) indicated a clear transition from dividing MEFs to differentiated cardiomyocyte-like state in CiCM samples.
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Project description:Exclusion of Parkin from mitochondria of perinatal cardiomyocytes interrupts structural and molecular transformations essential to normal perinatal-adult mitochondrial replacement. mRNA-sequencing from cardiac total RNA was performed at P1, P21 and 5-week stages of nontransgenic (ntg) and human-Mfn2-overexpressing (Mfn2wt) hearts, and also of tet-off control (tetoff) and human-Mfn2 T111A/S442A-overexpressing (Mfn2AA) hearts.
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Project description:Birth is the first metabolic challenge that cardiomyocytes need to overcome as they reshape their fuel preference from glucose to fatty acids (FA) to optimize energy production in postnatal life. This adaptation is partly triggered by drastic post-partum environmental changes, yet the molecular players responsible for orchestrating cardiomyocyte maturation remain unknown. Here, we discover that maternal metabolite γ-linolenic acid (GLA) support this transition. Specifically, colostrum GLA acts as an agonist for Retinoid X Receptors (RXR), a family of ligand-activated transcription factors expressed from embryonic life in cardiomyocytes. Mice lacking RXR in embryonic cardiomyocytes showed an aberrant chromatin landscape that prevented the induction of RXR-dependent FA metabolism genes (mtFAH signature). This results in a defective metabolic transition with blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, which ultimately leads to perinatal lethal cardiac dysfunction. In vitro GLA supplementation in cardiomyocytes induced the expression of mtFAH signature in a RXR-dependent manner. Altogether, our study uncovers GLA/RXR axis as the fundamental mechanism by which maternal physiology commands metabolic functioning in perinatal hearts. This SuperSeries is composed of the SubSeries listed below.
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