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Series GSE51921 Query DataSets for GSE51921
Status Public on Dec 01, 2015
Title DNA methylation analysis in idiopathic and LRRK2-associated Parkinson's disease (PD)
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary We performed a genome-wide DNA methylation study in induced pluripotent stem cells (IPSC)-derived dopaminergic neurons (DAn) generated from keratinocytes of monogenic and sporadic Parkinson disease (PD) patients as well as of healthy subjects. We observed extensive DNA methylation changes in DAn from PD patients. These changes were neither present in the original keratinocytes nor in the undifferentiated IPSCs, suggesting latent molecular defects in PD keratinocytes that are manifested only upon differentiation into DAn. We also found that enhancers showing abnormal DNA hypermethylation in PD were enriched for binding sites of transcription factors such as FOXA1, NR3C1, HNF4A and FOSL2 which are involved in the survival of DAn and showed reduced expression. These data suggest that aberrant epigenomic remodeling of IPSC-derived DAn in PD is mediated by the down-regulation of key transcription factors. Our study suggests that future cell replacement strategies should pay careful attention to the correct epigenomic status of the reprogrammed cells, especially when using patient own skin cells.
Overall design Number of samples analyzed: 14 iPSC-derived dopaminergic neurons, 7 fibroblasts and 7 IPSCs. Control (C) samples, no pathological changes: SP-09, SP-11 SP-15 SP-17. Samples from idiopathic Parkinson's Disease (IPD) patients: SP-01, SP-02, SP-04, SP-08, SP-10, SP-16. Samples from Parkinson's disease patients carriers of G2019S LRRK2 mutation (MPD): SP-05, SP-06, SP-12, SP-13. No replicates. iPSC: induced pluripotent stem cells. FIB: fibroblasts. HumanMethylation 450K BeadChip Kit (Illumina Inc., CA, USA) were used to analyse DNA methylation.
Contributor(s) Ezquerra M, Fernandez-Santiago R, Tolosa E, Sànchez-Pla À, Mosquera JL
Citation(s) 26516212
Submission date Oct 30, 2013
Last update date Mar 22, 2019
Contact name Mario Ezquerra
Phone 0034 932273122
Organization name Fundacio Clinic/IDIBAPS
Department Neurology
Lab Neurodegenerative Diseases
Street address Villarroel 170
City Barcelona
State/province Catalonia
ZIP/Postal code 08027
Country Spain
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (28)
GSM1255293 genomic DNA from IPSC-derived DAn SP-09-CON
GSM1255294 genomic DNA from IPSC-derived DAn SP-11-CON
GSM1255295 genomic DNA from IPSC-derived DAn SP-15-CON
This SubSeries is part of SuperSeries:
GSE51923 Idiopathic and LRRK2-associated Parkinson's disease
BioProject PRJNA225815

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE51921_RAW.tar 183.1 Mb (http)(custom) TAR
GSE51921_signal_intensities.txt.gz 122.9 Mb (ftp)(http) TXT
Processed data included within Sample table

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