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2015-10-29

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cc-by (c) Fernández Santiago, Rubén et al., 2015
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/188109

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients

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https://doi.org/10.15252/emmm.201505439

Abstract

The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and a transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic PD (sPD), and healthy subjects. We observed extensive DNA methylation changes in PD DAn, and of RNA expression, which were common in L2PD and sPD. No significant methylation differences were present in parental skin cells, undifferentiated iPSCs nor iPSC-derived neural cultures not-enriched-in-DAn. These findings suggest the presence of molecular defects in PD somatic cells which manifest only upon differentiation into the DAn cells targeted in PD. The methylation profile from PD DAn, but not from controls, resembled that of neural cultures not-enriched-in-DAn indicating a failure to fully acquire the epigenetic identity own to healthy DAn in PD. The PD-associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the RNA and/or protein downregulation of a network of transcription factors relevant to PD (FOXA1, NR3C1, HNF4A, and FOSL2). Using a patient-specific iPSC-based DAn model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD.

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Malaltia de Parkinson, ADN

Subject (English)

Parkinson's disease, DNA

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citation

FERNÁNDEZ SANTIAGO, Rubén, et al. Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients. EMBO Molecular Medicine. 2015. Vol. 7, num. 12, pags. 1529-1546. ISSN 1757-4676. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/188109

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