The Transcriptional Landscape of Regenerating Newborn Mouse Hearts

Dobreva, Gergana; Braun, Thomas

doi:10.1161/circresaha.115.305918

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Recent global expression profiling of developing heart tissues revealed general upregulation of sarcomeric and mitochondrial proteins after birth [16]. Likewise, our quantitative proteomics study showed clear upregulation of those compartments.…”

Section: Perm1 Is Upregulated During Early Heart Development From P2-p20supporting

confidence: 74%

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein

Aravamudhan¹,

Türk

Bock

et al. 2021

Journal of Molecular and Cellular Cardiology

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Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1-and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein kinase 2. Ablation of Perm1 in mice results in reduced protein expression of lipin-1 accompanied by accumulation of specific phospholipid species. Isolation of Perm1-deficient mitochondria revealed significant downregulation of mitochondrial transport proteins for amino acids and carnitines, including SLC25A12/13/29/34 and CPT2. Consistently, we observed altered levels of various lipid species, amino acids, and acylcarnitines in Perm1 − /− mitochondria. We conclude that the outer mitochondrial membrane protein PERM1 regulates homeostasis of lipid and amino acid metabolites in mitochondria.

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Section: Perm1 Is Upregulated During Early Heart Development From P2-p20supporting

confidence: 74%

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein

Aravamudhan¹,

Türk

Bock

et al. 2021

Journal of Molecular and Cellular Cardiology

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“…The copyright holder for this preprint this version posted May 18, 2023. ; https://doi.org/10. 1101 Transcriptomic studies have contributed fundamentally to our knowledge on myocardial remodeling in animal models of acute LHF and on human LHF, but key HF genes reported have been often inconsistent between studies (Dobreva & Braun, 2015;Joshi et al, 2021;O'Meara et al, 2015;Raghow, 2016). To resolve some of these issues, a recent meta-analysis curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts, collected during heart transplantation, left ventricular assist device implantation, or surgical ventricular restoration, to derive a consensus signature of LHF (Ramirez Flores et al, 2021).…”

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confidence: 99%

A common gene signature of the right ventricle in failing rat and human hearts

Jurida

Werner

Knapp

et al. 2023

Preprint

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The molecular mechanisms of progressive right heart failure are incompletely understood. We systematically compared rat models of pulmonary artery or aortic banding to identify the transcriptomic changes that occur over months in the failing right versus left ventricle. Detailed bioinformatics analyses of 181 RNAseq datasets from cardiomyocytes or whole heart samples from these models, led to the identification of gene signatures, protein, and transcription factor networks specific to ventricles, compensated or decompensated disease states and type of heart failure. RNA-FISH approaches confirmed PAB-mediated regulation of key genes and revealed striking, spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with 95 transcriptome data sets from human patients with chronic thromboembolic pulmonary hypertension led to the identification of more than 50 genes whose expression levels strongly correlated with the severity of right heart disease. Together, these data define a conserved, differentially regulated genetic network that coordinates progressive right heart failure in rats and humans.

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The Transcriptional Landscape of Regenerating Newborn Mouse Hearts

Cited by 2 publications

References 17 publications

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein

A common gene signature of the right ventricle in failing rat and human hearts

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