Pluto Bioinformatics

GSE74201: Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in a Human Neural Stem Cell Model of Huntingtons Disease

Bulk RNA sequencing

We have utilized induced pluripotent stem cells (iPSCs) derived from Huntingtons disease patients (HD iPSCs) as a human model of HD and determined that the disease phenotypes only manifest in the differentiated neural stem cell (NSC) stage, not in iPSCs. To understand the molecular basis for the CAG repeat expansion dependent disease phenotypes in NSCs, we performed transcriptomic analysis of HD iPSCs and HD NSCs compared to isogenic controls using RNA-Seq. Differential gene expression and pathway analysis pointed to TGF-b and netrin-1 as the top dysregulated pathways. Using data driven gene coexpression network analysis, we identified seven distinct coexpression modules, and focused on two that were correlated with changes in gene expression in NSC due to the CAG expansion. Strikingly, our HD NSC model revealed the dysregulation of genes involved in neuronal development and the formation of the dorsal striatum in HD. Further, the striatal specific and neuronal networks disrupted could be modulated to correct HD phenotypes and provide novel therapeutic targets for HD SOURCE: Giovanni Coppola (gcoppola@ucla.edu) - Neurogenetics UCLA