Details

Autor(en) / Beteiligte

• Roessler, Reinhard
• Smallwood, Sebastien A.
• Veenvliet, Jesse V.
• Pechlivanoglou, Petros
• Peng, Su-Ping
• Chakrabarty, Koushik
• Groot-Koerkamp, Marian J.A.
• Pasterkamp, R. Jeroen
• Wesseling, Evelyn
• Kelsey, Gavin
• Boddeke, Erik
• Smidt, Marten P.
• Copray, Sjef

Titel

Detailed Analysis of the Genetic and Epigenetic Signatures of iPSC-Derived Mesodiencephalic Dopaminergic Neurons

Ist Teil von

• Stem cell reports, 2014-04, Vol.2 (4), p.520-533

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 (Pitx3Gfp/+) neurons derived from mouse iPSCs and primary mdDA (Pitx3Gfp/+) 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. •Purification of iPSC-derived mdDA neurons and primary embryonic mdDA neurons•Comparative gene-expression profiling and DNA methylation mapping of mdDA neurons•High similarity but also differences between primary and iPSC-derived mdDA neurons•Differences mainly in genes involved in neuron differentiation and development In this study, Copray and colleagues provide a detailed in-depth characterization of purified iPSC-derived dopaminergic neurons. Global epigenetic and genetic comparisons with freshly isolated mouse midbrain dopaminergic neurons identified potentially crucial deviations in iPSC-derived neurons regarding DNA methylation and gene expression that may eventually influence unambiguous long-term functionality.