Journal
CLINICAL EPIGENETICS
Volume 11, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13148-019-0701-6
Keywords
Parkinson disease (PD); iPSC-derived DAn; DNA methylation; Whole-genome bisulfite sequencing (WGBS); DMCpGs; Differentially methylated CpGs
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Funding
- Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III (ISCIII) [PI14/00426]
- Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED) to the Movement Disorders Unit of the Neurology Service from the Hospital Clinic de Barcelona [PRI-16-2017]
- Jovenes Investigadores grant through the Programa Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad (Plan Estatal de I+D+I 2013-2016) of the Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2015-73508-JIN]
- Agencia Estatal de Investigacion (AEI)
- FEDER (AEI/FEDER/UE)
- European Research Council (ERC) 2012-StG [311736-PD-HUMMODEL]
- ISCIII/FEDER [RD16/0011/0024, PIE14/00061]
- Generalitat de Catalunya (iPS4BioMed SGR 2017-2019)
- [BFU2013-49157-P]
- [BFU2016-80870-P]
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BackgroundParkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons (DAn). Previously, we described the presence of DNA hyper- and hypo-methylation alterations in induced pluripotent stem cells (iPSC)-derived DAn from PD patients using the Illumina 450K arraywhich prominently covers gene regulatory regions.MethodsTo expand and contextualize previous findings, we performed the first whole-genome DNA bisulfite sequencing (WGBS) using iPSC-derived DAn from representative PD subjects: one sporadic PD (sPD) patient, one monogenic LRRK2-associated PD patient (L2PD), and one control.ResultsAt the whole-genome level, we detected global DNA hyper-methylation in the PD which was similarly spread across the genome in both sPD and L2PD and mostly affected intergenic regions.ConclusionThis study implements previous epigenetic knowledge in PD at a whole genome level providing the first comprehensive and unbiased CpG DNA methylation data using iPSC-derived DAn from PD patients. Our results indicate that DAn from monogenic or sporadic PD exhibit global DNA hyper-methylation changes. Findings from this exploratory study are to be validated in further studies analyzing other PD cell models and patient tissues.
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