Detailed Analysis of the Genetic and Epigenetic Signatures of iPSC-Derived Mesodiencephalic Dopaminergic Neurons
| Autor: | Jesse V. Veenvliet, R. Jeroen Pasterkamp, Sébastien A. Smallwood, Sjef Copray, Reinhard Roessler, Erik Boddeke, Marten P. Smidt, Gavin Kelsey, Su-Ping Peng, Marian J.A. Groot-Koerkamp, Evelyn Wesseling, Petros Pechlivanoglou, Koushik Chakrabarty |
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| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR), Translational Immunology Groningen (TRIGR), Kelsey, Gavin [0000-0002-9762-5634], Apollo - University of Cambridge Repository, Molecular Neuroscience (SILS, FNWI) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Nervous system
Cell type Induced Pluripotent Stem Cells Gene Expression Substantia nigra Mice Transgenic Biology Biochemistry Article Epigenesis Genetic Mice DNA DEMETHYLATION PARKINSONS-DISEASE Genetics medicine Animals Epigenetics PITX3 Induced pluripotent stem cell lcsh:QH301-705.5 TRANSGENIC MICE lcsh:R5-920 SUBSTANTIA-NIGRA Dopaminergic Neurons Gene Expression Profiling Dopaminergic METHYLATION Cell Biology DNA Methylation NERVOUS-SYSTEM Gene expression profiling medicine.anatomical_structure DIFFERENTIATION nervous system lcsh:Biology (General) Organ Specificity DNA methylation Transcriptome lcsh:Medicine (General) Neuroscience PLURIPOTENT STEM-CELLS Biomarkers HUMAN ES Developmental Biology |
| Zdroj: | Stem Cell Reports, Vol 2, Iss 4, Pp 520-533 (2014) Stem Cell Reports, 2(4), 520-533. CELL PRESS Stem Cell Reports, 2(4), 520-533. Cell Press Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • 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. |
| Databáze: | OpenAIRE |
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