Fernández-Santiago, RubenMerkel, AngelikaCastellano, GiancarloHeath, SimonRaya Chamorro, ÁngelTolosa, EduardMartí, Maria JoséConsiglio, AntonellaEzquerra, Mario2019-09-272019-09-272019Fernández-Santiago R, Merkel A, Castellano G, Heath S, Raya Á, Tolosa E, Martí MJ, Consiglio A, Ezquerra M. Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients. Clin Epigenetics. 2019; 11(1):108. DOI 10.1186/s13148-019-0701-61868-7075http://hdl.handle.net/10230/42348Background: 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.application/pdfeng© The Author(s). 2019. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13148-019-0701-6Parkinson disease (PD)iPSC-derived DAnDNA methylationWhole-genome bisulfite sequencing (WGBS)DMCpGsDifferentially methylated CpGsinfo:eu-repo/semantics/openAccess