Detailed Analysis of the Genetic and Epigenetic Signatures of IPSC-derived Mesodiencephalic Dopaminergic Neurons

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2014 Apr 22

PMID 24749075

Citations 22

Authors

Reinhard Roessler

Sebastien A Smallwood

Jesse V Veenvliet

Petros Pechlivanoglou

Su-Ping Peng

Koushik Chakrabarty

Marian J A Groot-Koerkamp

R Jeroen Pasterkamp

Evelyn Wesseling

Gavin Kelsey

Erik Boddeke

Marten P Smidt

Sjef Copray

Affiliations

Soon will be listed here.

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.

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