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| 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.
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| 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.
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| 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 |
| E-mail(s) |
ezquerra@clinic.cat
|
| 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 |
| |
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| 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 |
| GSM1255296 |
genomic DNA from IPSC-derived DAn SP-17-CON |
| GSM1255297 |
genomic DNA from IPSC-derived DAn SP-01-IPD |
| GSM1255298 |
genomic DNA from IPSC-derived DAn SP-02-IPD |
| GSM1255299 |
genomic DNA from IPSC-derived DAn SP-04-IPD |
| GSM1255300 |
genomic DNA from IPSC-derived DAn SP-08-IPD |
| GSM1255301 |
genomic DNA from IPSC-derived DAn SP-10-IPD |
| GSM1255302 |
genomic DNA from IPSC-derived DAn SP-16-IPD |
| GSM1255303 |
genomic DNA from IPSC-derived DAn SP-05-L2PD |
| GSM1255304 |
genomic DNA from IPSC-derived DAn SP-06-L2PD |
| GSM1255305 |
genomic DNA from IPSC-derived DAn SP-12-L2PD |
| GSM1255306 |
genomic DNA from IPSC-derived DAn SP-13-L2PD |
| GSM1255307 |
genomic DNA from IPSC IPSC.SP-09-CON |
| GSM1255308 |
genomic DNA from IPSC IPSC.SP-11-CON |
| GSM1255309 |
genomic DNA from IPSC IPSC.SP-17-CON |
| GSM1255310 |
genomic DNA from IPSC IPSC.SP-04-sPD |
| GSM1255311 |
genomic DNA from IPSC IPSC.SP-16-sPD |
| GSM1255312 |
genomic DNA from IPSC IPSC.SP-06-L2PD |
| GSM1255313 |
genomic DNA from IPSC IPSC.SP-13-L2PD |
| GSM1255314 |
genomic DNA from fibroblasts FIB-SP-09-CON |
| GSM1255315 |
genomic DNA from fibroblasts FIB-SP-11-CON |
| GSM1255316 |
genomic DNA from fibroblasts FIB-SP-17-CON |
| GSM1255317 |
genomic DNA from fibroblasts FIB-SP-04-sPD |
| GSM1255318 |
genomic DNA from fibroblasts FIB-SP-16-sPD |
| GSM1255319 |
genomic DNA from fibroblasts FIB-SP-06-L2PD |
| GSM1255320 |
genomic DNA from fibroblasts FIB-SP-13-L2PD |
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| This SubSeries is part of SuperSeries: |
| GSE51923 |
Idiopathic and LRRK2-associated Parkinson's disease |
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| Relations |
| BioProject |
PRJNA225815 |
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