Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of neural stem/progenitor cells (NS/PCs) in control and prenatal valproic acid (VPA) exposed mice with or without voluntary exercise

ABSTRACT: Purpose: The goals of this study are to investigate the effect of prenatal VPA exposure on transcriptome profile of NS/PCs during development, and the effect of exercise on transcriptome profile of adult NS/PCs in prenatal VPA exposed mice. Methods: NS/PCs mRNA profiles of embryonic day15 (E15), postnatal day5 (P5) and 12-week-old (12w) contol mice and E15, P5, 12w with or without voluntary exercise prenatal VPA exposed mice were generated by deep sequencing, in triplicate, using Illumina Hiseq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with a method: TopHat/Bowtie2 followed by Cufflinks.NS/PCs were isolated from forebrain (E15), hippocampal dentate gyrus (P5 and 12w) of Nestin-EGFP mice. Results: Hierarchial clustering using eighteen samples (E15 Ctrl, E15 VPA, P5 Ctrl, P5 VPA, 12w Ctrl, 12w VPA, three samples each) identified three distinct clusters composed of NS/PCs derived from each developmental stage. Gene set enrichment analysis using transcriptome of E15 Ctrl and E15 VPA revealed a significant increase in the expression of neuron differentiation- and nervous system development-related genes in VPA compared with Ctrl. Gene ontology analysis of biological processes using differentially expressed genesin 12w VPA compared with 12w Ctrl revealed that expression levels of cell-migration-associated genes were altered. Voluntary running mostly amended both positively and negativly distorted gene expression in the 12w VPA compared with 12w Ctrl NS/PCs. The altered expression of cell migration-related genes was largely normalized by voluntary running.

ORGANISM(S): Mus musculus

PROVIDER: GSE101239 | GEO | 2018/03/15

REPOSITORIES: GEO