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Stem Cell Reports. 2014 Apr 3;2(4):520-33. doi: 10.1016/j.stemcr.2014.03.001. eCollection 2014.

Detailed analysis of the genetic and epigenetic signatures of iPSC-derived mesodiencephalic dopaminergic neurons.

Author information

  • 1Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, 9713AV Groningen, the Netherlands.
  • 2Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
  • 3Center for Neuroscience, Swammerdam Institute for Life Science, Science Park Amsterdam, 1098XH Amsterdam, the Netherlands.
  • 4Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, 9713AV Groningen, the Netherlands.
  • 5Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
  • 6Molecular Cancer Research, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.

Abstract

Induced pluripotent stem cells (iPSCs) hold great promise for in vitro generation of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA) neurons involved in Parkinson's disease. Although iPSC-derived midbrain DA neurons have been generated, detailed genetic and epigenetic characterizations of such neurons are lacking. The goal of this study was to examine the authenticity of iPSC-derived DA neurons obtained by established protocols. We FACS purified mdDA (Pitx3 (Gfp/+) ) neurons derived from mouse iPSCs and primary mdDA (Pitx3 (Gfp/+) ) neurons to analyze and compare their genetic and epigenetic features. Although iPSC-derived DA neurons largely adopted characteristics of their in vivo counterparts, relevant deviations in global gene expression and DNA methylation were found. Hypermethylated genes, mainly involved in neurodevelopment and basic neuronal functions, consequently showed reduced expression levels. Such abnormalities should be addressed because they might affect unambiguous long-term functionality and hamper the potential of iPSC-derived DA neurons for in vitro disease modeling or cell-based therapy.

PMID:
24749075
PMCID:
PMC3986662
DOI:
10.1016/j.stemcr.2014.03.001
[PubMed - indexed for MEDLINE]
Free PMC Article
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