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RNA-Seq transcriptome profiling of embryonic age 17.5 or E17.5 ventricles of cardiac specific-estrogen-related receptor alpha and gamma (ERRa/g) knock out (KO) mouse generated by Nkx2.5-Cre driver and its control wild type.

ABSTRACT: Transcriptional regulatory circuits that drive cardiomyocyte maturation during the developmental process are poorly understood. Estrogen-related receptor alpha and gamma (ERRa/g) have been shown to be involved in all aspects of mitochondrial energy production. However, the function of ERR during the cardiac developmental process is not understood well. To examine the role of (ERRa/g), we generated cardiac-specific ERRa/g knockout (KO) mice and found that the KO mice died within 24 hours post-birth. At embryonic age 17.5, a number of genes involved in oxidative mitochondrial metabolism including OXPHOS, TCA cycle, and fatty acid oxidation were dramatically downregulated. Also, the mutant hearts exhibited a significant downregulation of adult cardiac contractile protein, ion channel and Ca2+ handling genes. In contrast, fetal cardiac genes and non-cardiac genes that express in fibroblast or endothelial cells were ectopically induced in the KO hearts. These results suggest that ERRa/g are essential factors for the broad cardiomyocyte maturation program.

ORGANISM(S): Mus musculus

PROVIDER: GSE113761 | GEO | 2020/06/10

REPOSITORIES: GEO

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RNA-Seq transcriptome profiling of postnatal age 35 days or P35 ventricles of cardiac-specific estrogen-related receptor alpha and gamma (ERRa/g) knock down (KD) mouse generated by AAV-cTnT-Cre injection and its control AAV-Luc injection.

Project description:Transcriptional regulatory circuits that drive cardiomyocyte maturation during the developmental process are poorly understood. Estrogen-related receptor alpha and gamma (ERRa/g) have been shown to be involved in all aspects of mitochondrial energy production. However, the function of ERR during the postnatal cardiac developmental process is unclear. To examine the role of (ERRa/g) during postnatal cardiac maturation, we generated inducible cardiac-specific ERRa/g knockdown (KD) mice with adeno-associated virus serotype 9 (AAV9) expressing Cre. We found that at P35 a number of genes involved in oxidative mitochondrial metabolism including OXPHOS, TCA cycle, branched chain amino acid catabolism, and fatty acid oxidation were dramatically downregulated. Also, the KD hearts exhibited a significant downregulation of adult cardiac contractile protein, ion channel and Ca2+ handling genes. In contrast, fetal cardiac genes and non-cardiac genes that express in fibroblast or skeletal muscle cells were ectopically induced in the KD hearts. These results suggest that ERRa/g are essential factors for the broad postnatal cardiomyocyte maturation program.

2020-06-10 | GSE135347 | GEO

ERRa/ERRg KO heart gene expression analysis

Project description:ERRa and ERRg are essential transcriptional regulators of cardiac metabolism and functions. Here we extend our previous studies by analyzing the transcriptome changes in ERRa/ERRg KO hearts

2017-05-05 | GSE88761 | GEO

RNA-Seq transcriptome profiling of estrogen-related receptor alpha and gamma (ERRa/g) knock out (KO) human iPS cell-derived cardiomyocytes (hiPSC-CMs)

Project description:Transcriptional regulatory circuits that drive cardiomyocyte maturation are poorly understood. Here we found that in ERRa/g KO hiPSC-CMs, cardiac energy metabolic and cardiac structural transcriptional programs are dysregulated.

2022-02-16 | GSE165963 | GEO

Transcription profiling of mouse ERRalpha wild type vs. knockout hearts, baseline

Project description:We hypothesized that the estrogen-related receptor a (ERRa), which recruits PGC-1a to metabolic target genes in heart, exerts protective effects in the context of stressors known to cause heart failure. ERRa-/- mice subjected to left ventricular (LV) pressure overload developed signatures of heart failure including chamber dilatation and reduced LV fractional shortening. 31P-NMR studies revealed abnormal phosphocreatine depletion in ERRa-/- hearts subjected to hemodynamic stress, indicative of a defect in ATP reserve. Mitochondrial respiration studies demonstrated reduced maximal ATP synthesis rates in ERRa-/- hearts. Cardiac ERRa target genes involved in energy substrate oxidation, ATP synthesis, and phosphate transfer were downregulated in ERRa-/- mice at baseline or with pressure overload. These results demonstrate that ERRa, a potential therapeutic target, is indispensable for the adaptive bioenergetic response to hemodynamic stressors known to cause heart failure. Experiment Overall Design: Microarray analyses were performed with two samples each of ERRawt and ERRako to compare baseline changes in gene expression. Validation real-time PCR (n=7) was subsequently performed to characterize expression changes of gene targets identified in microarray and ChIP-chip studies in hearts of ERRa wt and KO mice at baseline and subjected to pressure overload stress.

2008-06-15 | E-GEOD-8106 | biostudies-arrayexpress

Differential gene expression between WT and ERRa-null hearts

Project description:Total RNA was isolated from 3 WT and 3 ERRa null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa. Keywords: microarray and genetic modification

2007-03-08 | GSE7196 | GEO

Assay for transposase-accessible chromatin sequencing (ATAC-seq) on estrogen-related receptor alpha and gamma (ERRa/g) knock out (KO) human iPS cell-derived cardiomyocytes (hiPSC-CMs)

Project description:To determine the role of estrogen-related receptor alpha and gamma (ERRa/g) on chromatin accessibility, we performed ATAC-seq studies with WT control and ERRa/g KO hiPSC-CMs. We found that ERRa/g activates cardiac chromatin accessibilities in hiPSC-CMs. A subset of the decreased ATAC signals by loss of ERRa/g overlapped ERRg peaks (GSE113760) in hiPSC-CMs, suggesting that ERRg might be directly involved in the activation of cardiac chromatin accessibilities. The motif analysis with decreased ATAC signal by loss of ERRa/g revealed that cardiac-enriched transcription factors such as MEF2 and GATA could cooperate with ERR.

2022-02-16 | GSE165962 | GEO

Single cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

Project description:Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon coculture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.

2020-04-20 | GSE122706 | GEO

ERRalpha wt vs. ko hearts, baseline

2007-10-16 | GSE8106 | GEO

Role of estrogen related receptor alpha (ERRa) in CD4+ T cell gene expression

Project description:ERRa is an orphan nuclear receptor with an established role in cell metabolism. Our studies demonstrate that acute or chronic loss of ERRa broadly affects mitochondrial and glycolytic metabolism in CD4+ T cells and results in diminished T cell function and differentation. In this array, we assessed the contribution of ERRa to changes in gene expression in resting and stimulated CD4+ T cells with the goal of identifying specific metabolic genes that exhibit altered expression in the presence or absence of ERRa. Please see related publication: Michalek, et al. PNAS 2011.

2011-10-21 | GSE33108 | GEO

Microarray of cardiac biventricle from PGC-1a-/-bf/f/MerCre mice

Project description:The following abstract from the submitted manuscript describes the major findings of this work. The metabolic development of high energy-utilizing organs such as the heart involves mitochondrial proliferation at birth followed by a maturation process during the postnatal period. Conditional gene targeting was used in mice to explore the role of the PPARgamma coactivator 1 (PGC-1) coactivators during postnatal development and in adult heart. Marked mitochondrial derangements were observed in hearts of PGC-1a/b-deficient mice during the postnatal period, including fragmentation and elongation associated with the development of a lethal cardiomyopathy. The expression of multiple genes involved in mitochondrial fusion and fission was downregulated in hearts of PGC-1a/b-deficient mice. PGC-la was shown to activate transcription of the mitofusin 1 (Mfn1) gene by coactivating the estrogen-related receptor a (ERRa) upon a highly conserved element. Surprisingly, PGC-1a/b deficiency did not alter cardiac function or general mitochondrial density and myocyte distribution in adult heart. However, transcriptional profiling and mitochondrial function studies demonstrated that the PGC-1 coactivators are required for full respiratory capacity and high level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial energy transduction and oxidative phosphorylation pathways in adult heart. These results unveil distinct developmental stage-specific transcriptional programs involved in the maturation and maintenance of mitochondria. RNA from five PGC-1a-/- and five PGC-1a-/-bf/f/MerCre mice was analyzed.

2014-01-13 | E-GEOD-43798 | biostudies-arrayexpress

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