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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Roessler, Reinhard 
Smallwood, Sebastien A 
Veenvliet, Jesse V 
Pechlivanoglou, Petros 
Peng, Su-Ping 

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.

Description

Keywords

Animals, Biomarkers, DNA Methylation, Dopaminergic Neurons, Epigenesis, Genetic, Gene Expression, Gene Expression Profiling, Induced Pluripotent Stem Cells, Mice, Mice, Transgenic, Organ Specificity, Transcriptome

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

2

Publisher

Elsevier BV