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Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

ABSTRACT: Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

PROVIDER: PRJNA421308 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6353580_1.fastq.gz	Fastqsanger.gz
	SRR6353580_2.fastq.gz	Fastqsanger.gz
	SRR6353581_1.fastq.gz	Fastqsanger.gz
	SRR6353581_2.fastq.gz	Fastqsanger.gz
	SRR6353582_1.fastq.gz	Fastqsanger.gz

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Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach.

Project description:The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and β-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.

| S-EPMC5904546 | biostudies-literature

Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

Project description:The heart of new-born mouse has exceptional capacity to regenerate from myocardial injury. However, the mouse heart loses this capacity within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during the loss of its regenerative potential, a systematic comparison of 1-day and 7-day-old mouse hearts was performed at the proteomic, metabolomic, and transcriptomic levels.

2018-12-01 | GSE107760 | GEO

Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics

Project description:Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [spatial]

Project description:Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [spatial]

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Parallel single cell multi-omics analysis of neonatal skin reveals transitional fibroblast states that restrict differentiation into distinct fates

Project description:One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multi-omics analysis by processing neonatal murine skin for single-cell ATAC-sequencing (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages based on transcriptome profiling, as previously published. However, scATAC-seq analysis of neonatal fibroblast lineage markers, such as, Dpp4/CD26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage specific transcriptome profiles. These results suggests that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary, reticular, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our scATAC-seq analysis also revealed that the functional lineage restriction between dermal papilla and adipocytes fates are regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multi-omics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [RNA-seq]

Project description:Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [RNA-seq]

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [spatial]

Project description:We use spatial transcriptomics to establish regional transcriptional profile of neonatal heart tissue obtained at indicated timpoints after apical resection surgery.

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Simultaneous Metabolite, Protein, Lipid Extraction (SIMPLEX): A Combinatorial Multimolecular Omics Approach for Systems Biology.

Project description:Interconnected molecular networks are at the heart of signaling pathways that mediate adaptive plasticity of eukaryotic cells. To gain deeper insights into the underlying molecular mechanisms, a comprehensive and representative analysis demands a deep and parallel coverage of a broad spectrum of molecular species. Therefore, we introduce a simultaneous metabolite, protein, lipid extraction (SIMPLEX) procedure, a novel strategy for the quantitative investigation of lipids, metabolites, and proteins. Compared with unimolecular workflows, SIMPLEX offers a fundamental turn in study design since multiple molecular classes can be accessed in parallel from one sample with equal efficiency and reproducibility. Application of this method in mass-spectrometry-based workflows allowed the simultaneous quantification of 360 lipids, 75 metabolites, and 3327 proteins from 10(6)cells. The versatility of this method is shown in a model system for adipogenesis- peroxisomal proliferator-activated receptor gamma (PPARG) signaling in mesenchymal stem cells-where we utilized SIMPLEX to explore cross-talk within and between all three molecular classes and identified novel potential molecular entry points for interventions, indicating that SIMPLEX provides a superior strategy compared with conventional workflows.

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