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

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 whic...

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Detalles Bibliográficos
Autores: Fernández Santiago, Rubén, Merkel, Angelika, Castellano, Giancarlo, Heath, Simon, Raya Chamorro, Ángel, Tolosa, Eduardo, Martí Domènech, Ma. Josep, Consiglio, Antonella, Ezquerra Trabalón, Mario
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171541
Acceso en línea:https://hdl.handle.net/2445/171541
Access Level:acceso abierto
Palabra clave:Malaltia de Parkinson
ADN
Metilació
Parkinson's disease
DNA
Methylation
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spelling Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patientsFernández Santiago, RubénMerkel, AngelikaCastellano, GiancarloHeath, SimonRaya Chamorro, ÁngelTolosa, EduardoMartí Domènech, Ma. JosepConsiglio, AntonellaEzquerra Trabalón, MarioMalaltia de ParkinsonADNMetilacióParkinson's diseaseDNAMethylationBackground: 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.BioMed Central2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion7 p.application/pdfhttps://hdl.handle.net/2445/171541Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s13148-019-0701-6Clinical Epigenetics, 2019, vol. 11https://doi.org/10.1186/s13148-019-0701-6info:eu-repo/grantAgreement/EC/FP7/311736cc-by (c) Fernández Santiago, Rubén et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1715412026-05-29T05:05:01Z
dc.title.none.fl_str_mv Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
title Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
spellingShingle Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
Fernández Santiago, Rubén
Malaltia de Parkinson
ADN
Metilació
Parkinson's disease
DNA
Methylation
title_short Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
title_full Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
title_fullStr Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
title_full_unstemmed Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
title_sort Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients
dc.creator.none.fl_str_mv Fernández Santiago, Rubén
Merkel, Angelika
Castellano, Giancarlo
Heath, Simon
Raya Chamorro, Ángel
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Consiglio, Antonella
Ezquerra Trabalón, Mario
author Fernández Santiago, Rubén
author_facet Fernández Santiago, Rubén
Merkel, Angelika
Castellano, Giancarlo
Heath, Simon
Raya Chamorro, Ángel
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Consiglio, Antonella
Ezquerra Trabalón, Mario
author_role author
author2 Merkel, Angelika
Castellano, Giancarlo
Heath, Simon
Raya Chamorro, Ángel
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Consiglio, Antonella
Ezquerra Trabalón, Mario
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia de Parkinson
ADN
Metilació
Parkinson's disease
DNA
Methylation
topic Malaltia de Parkinson
ADN
Metilació
Parkinson's disease
DNA
Methylation
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/171541
url https://hdl.handle.net/2445/171541
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13148-019-0701-6
Clinical Epigenetics, 2019, vol. 11
https://doi.org/10.1186/s13148-019-0701-6
info:eu-repo/grantAgreement/EC/FP7/311736
dc.rights.none.fl_str_mv cc-by (c) Fernández Santiago, Rubén et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fernández Santiago, Rubén et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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