Web of Science: 59 citations, Scopus: 62 citations, Google Scholar: citations,
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 i Vié, 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 2020-05-11



   Favorit i Compartir