RNA-Seq Mouse Brain Regions Expression Data Analysis: Focus on ApoE Functional Network

J Integr Bioinform. 2017 Sep 13;14(3):20170024. doi: 10.1515/jib-2017-0024.

Abstract

ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007) and defeated (FDR < 0.001) mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc) gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.

Keywords: ApoE; App; Pomc; RNA-Seq data; Tomm40; brain lipid metabolism; brain regions; differentially expressed genes; gene expression profile; hypothalamus; social stress mouse model.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Aggression
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism*
  • Brain / metabolism*
  • Chronic Disease
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Genome / genetics
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Pro-Opiomelanocortin / genetics
  • RNA / analysis
  • RNA / genetics
  • Receptors, Lipoprotein / genetics
  • Sequence Analysis, RNA*
  • Stress, Psychological / genetics*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • Receptors, Lipoprotein
  • RNA
  • Pro-Opiomelanocortin
  • sortilin