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Aberrant epigenome in ‐derived dopaminergic neurons from Parkinson's disease patients
Fernández‐Santiago, Rubén (Universitat de Barcelona)
Carballo‐Carbajal, Iria (Vall d'Hebron Institut de Recerca (VHIR))
Castellano, Giancarlo (Universitat de Barcelona. Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Torrent, Roger (Universitat de Barcelona. Institut de Biomedicina (IBUB))
Richaud, Yvonne (Biomaterials and Nanomedicine (CIBER‐BBN). Centre for Networked Biomedical Research on Bioengineering)
Sánchez‐Danés, Adriana (Universitat de Barcelona. Institut de Biomedicina (IBUB))
Vilarrasa‐Blasi, Roser (Universitat de Barcelona. Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Sánchez‐Pla, Alex (Vall d'Hebron Institut de Recerca (VHIR))
Mosquera, José Luis (Universitat de Barcelona)
Soriano, Jordi (Universitat de Barcelona)
López‐Barneo, José (Universidad de Sevilla. Hospital Universitario Virgen del Rocío.)
Canals, Josep M (Universitat de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Alberch, Jordi (Universitat de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Raya, Ángel (Institució Catalana de Recerca i Estudis Avançats (ICREA))
Vila Bover, Miquel (Vall d'Hebron Institut de Recerca (VHIR))
Consiglio, Antonella (University of Brescia and National Institute of Neuroscience)
Martín‐Subero, José I (Universitat de Barcelona. Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Ezquerra, Mario (Universitat de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS))
Tolosa, Eduardo (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED))
Universitat Autònoma de Barcelona

Date: 2015
Abstract: The epigenomic landscape of Parkinson's disease () remains unknown. We performed a genomewide methylation and a transcriptome studies in induced pluripotent stem cell ()‐derived dopaminergic neurons (n) generated by cell reprogramming of somatic skin cells from patients with monogenic 2‐associated (L2) or sporadic (), and healthy subjects. We observed extensive methylation changes in n, and of expression, which were common in L2 and . No significant methylation differences were present in parental skin cells, undifferentiated s nor ‐derived neural cultures not‐enriched‐in‐n. These findings suggest the presence of molecular defects in somatic cells which manifest only upon differentiation into the n cells targeted in . The methylation profile from n, but not from controls, resembled that of neural cultures not‐enriched‐in‐n indicating a failure to fully acquire the epigenetic identity own to healthy n in . The ‐associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the and/or protein downregulation of a network of transcription factors relevant to (1, 3C1, 4A, and 2). Using a patient‐specific ‐based n model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD.
Note: Número d'acord de subvenció MINECO/FIS2010/21924-C02-02
Note: Número d'acord de subvenció AGAUR/2009/SGR-14
Note: Número d'acord de subvenció ISCIII/SAF2012/33526
Note: Número d'acord de subvenció ISCIII/PIE14/00061
Note: Número d'acord de subvenció ISCIII/BFU2013/49157-P
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Methylation ; Dopaminergic neuron ; Induced pluripotent stem cell ; Parkinson's disease ; Transcription factor ; Chromatin, Epigenetics, Genomics & Functional Genomics ; Neuroscience ; Stem Cells
Published in: EMBO Molecular Medicine, Vol. 7, Núm. 12 (October 2015) , p. 1529-1546, ISSN 1757-4684

PMID: 26516212
DOI: 10.15252/emmm.201505439


18 p, 2.2 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2018-01-31, last modified 2019-05-18



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