Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients

Background: Parkinson'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 array whic...

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Bibliographic Details
Authors: Fernández Santiago, Rubén, Merkel, Angelika, Castellano, Giancarlo, Heath, Simon, Raya Chamorro, Ángel, Tolosa, Eduardo, Martí Domènech, Ma. Josep, Consiglio, Antonella, Ezquerra Trabalón, Mario
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171541
Online Access:https://hdl.handle.net/2445/171541
Access Level:Open access
Keyword:Malaltia de Parkinson
ADN
Metilació
Parkinson's disease
DNA
Methylation
Description
Summary:Background: Parkinson'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 array which prominently covers gene regulatory regions. Methods: To 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. Results: At 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. Conclusion: This 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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