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Title: Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
Author: Fernández Santiago, Rubén
Merkel, Angelika
Castellano, Giancarlo
Heath, Simon
Raya Chamorro, Ángel
Tolosa, Eduardo
Marti, Maria Jose
Consiglio, Antonella
Ezquerra, Mario
Keywords: Malaltia de Parkinson
Parkinson's disease
Issue Date: 23-Jul-2019
Publisher: BioMed Central
Abstract: 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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It is part of: Clinical Epigenetics, 2019, vol. 11
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ISSN: 1868-7075
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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