Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system

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Title
Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system
Author(s)
H Park; H Kim; J Yoo; J Lee; H Choi; S Baek; C J Lee; Janghwan Kim; C J Lengner; J S Sung; J Kim
Bibliographic Citation
Biomaterials, vol. 72, pp. 152-162
Publication Year
2015
Abstract
Recent work generating induced dopaminergic (iDA) neurons using direct lineage reprogramming potentially provides a novel platform for the study and treatment Parkinson's disease (PD). However, one of the most important issues for iDA-based applications is the degree to which iDA neurons resemble the molecular and functional properties of their endogenous DA neuron counterparts. Here we report that the homogeneity of the reprogramming gene expression system is critical for the generation of iDA neuron cultures that are highly similar to endogenous DA neurons. We employed an inducible system that carries iDA-inducing factors as defined transgenes for direct lineage reprogramming to iDA neurons. This system circumvents the need for viral transduction, enabling a more efficient and reproducible reprogramming process for the generation of genetically homogenous iDA neurons. We showed that this inducible system generates iDA neurons with high similarity to their bona fide in vivo counterparts in comparison to direct infection methods. Thus, our results suggest that homogenous expression of exogenous genes in direct lineage reprogramming is critical for the generation of high quality iDA neuron cultures, making such culture systems a valuable resource for iDA-based drug screening and, ultimately, potential therapeutic intervention in PD.
Keyword
Direct lineage reprogrammingGene expression systemInduced neurons
ISSN
0142-9612
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.biomaterials.2015.09.002
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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