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Series GSE46798 Query DataSets for GSE46798
Status Public on Dec 05, 2013
Title Gene expression of A53T and corrected IPSC driven to DA neurons and exposed to paraquat and maneb
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Parkinson disease (PD) is characterized by extensive loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). A strong association has been reported between PD and exposure to mitochondrial toxins such as the environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived, stem cell model of PD that allows comparison of -synuclein ( -syn) mutant cells and isogeneic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations specific to A53T -syn mutant A9-DA neurons (hNs). We report a novel molecular pathway whereby basal as well as toxin-induced oxidative and nitrosative stress inhibits the MEF2C-PGC1 transcription network in A53T hNs compared to corrected controls, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small molecule high-throughput screening, we identify the MEF2C-PGC1 pathway as a new drug target for therapeutic benefit in PD.
Overall design In the current study, isogenic hiPSCs differing exclusively at a single amino acid (A53T) were exposed to either 2.8uM paraquat in combination with 1uM maneb for 24h or PBS vehicle control. Gene expression profile was analysed to assess the effect of both the genotype and exposure regiment on gene expression.
Contributor(s) Ryan S, Lipton S, Ambasudan R
Citation(s) 24290359
Submission date May 09, 2013
Last update date Aug 13, 2018
Contact name Scott Ryan
Organization name SBMRI
Street address 10901 North Torrey Pines Road
City La Jolla
ZIP/Postal code 92037
Country USA
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (12)
GSM1138502 Corr 1
GSM1138503 Corr 2
GSM1138504 Corr 3
BioProject PRJNA202312

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Supplementary file Size Download File type/resource
GSE46798_RAW.tar 26.2 Mb (http)(custom) TAR
GSE46798_non-normalized.txt.gz 4.9 Mb (ftp)(http) TXT
Raw data is available on Series record
Processed data included within Sample table

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