Aberrant epigenome in -derived dopaminergic neurons from Parkinson's disease patients
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-associa...
| Autores: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:185461 |
| Acesso em linha: | https://ddd.uab.cat/record/185461 https://dx.doi.org/urn:doi:10.15252/emmm.201505439 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Methylation Dopaminergic neuron Induced pluripotent stem cell Parkinson's disease Transcription factor Chromatin, Epigenetics, Genomics & Functional Genomics Neuroscience Stem Cells |
| Resumo: | 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. |
|---|