Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in a Human Neural Stem Cell Model of Huntingtons Disease
Transcriptomics Dataset
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General Information
AccessionGSE74201
TitleGenomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in a Human Neural Stem Cell Model of Huntingtons Disease
DescriptionWe 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
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74201
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Canned Analyses generated with the dataset

Dataset Accession
Tool Name

Interactive heatmap visualization of RNA-seq dataset GSE74201
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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