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2019-07-23

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cc-by (c) Fernández Santiago, Rubén et al., 2019
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/171541

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

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https://doi.org/10.1186/s13148-019-0701-6

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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Malaltia de Parkinson, ADN, Metilació

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Parkinson's disease, DNA, Methylation

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Publicacions de projectes de recerca finançats per la UE

Citation

FERNÁNDEZ SANTIAGO, Rubén, et al. Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients. Clinical Epigenetics. 2019. Vol. 11. ISSN 1868-7075. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/171541

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