Genetic regulation of succinate metabolism in the hypoxic heart of neonatal mice revealed by bulk and single-nucleus RNA sequencing analysis

PERALTA, TOMÁS M.; NUÑEZ PEDROZO, CRISTIAN N.; ULLA, SEBASTIÁN; LOCATELLI, PAOLA; OLEA, FERNANDA D.; CROTTOGINI, ALBERTO; CUNIBERTI, LUIS

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias.; 2022

Objective: The aim of this research was to compare the expression profile of genes related to succinate metabolism in the infarcted hearts of neonatal and infant mice by bulk and single-nucleus RNASeq analysis in order to clarify the molecular basis of the metabolic switch related to myocardial regeneration. Materials and methods: The bulk and single nucleus RNA-Seq files were retrieved from GEO (GSE142366). The heart samples were taken at 1.5, 3 and 7 days post-acute myocardial infarction (AMI) for neonatal (P1) and infant mice (P8). The bulk files were processed on UseGalaxy employing the FastQC/HISAT/featurecount pipeline. Differential gene expression analysis of bulk and single nucleus data was performed with edgeR and Seurat respectively. Results: Bulk analysis showed that at 1.5 days post AMI, neonatal mice had significant downregulation of the Krebs cycle genes Sucla2 (logFC -1.47), Sdha (logFC -1.20),Sdhb (logFC -0.81), Sdhd (logFC -0.78) and Succinate exporters genes Vdac1 (logFC -0.81), Slc16a1 (logFC -0.96) when compared to the infant mice (p < 0.001). At 7 days post AMI, neonatal miceshowed significant downregulation of Sucla2 (logFC -0.88), Sdha (logFC -0.48), Vdac1 (logFC -0.54) and Slc16a1 (logFC -0.90) compared to infant mice (p