Park, Hanseul Kim, Hongwon Yoo, Junsang Lee, Jaekwang Choi, Hwan Baek, Soonbong Lee, C. Justin Kim, Janghwan Lengner, Christopher J. Sung, Jung-Suk Kim, Jongpil 2024-01-20T05:32:26Z 2024-01-20T05:32:26Z 2021-09-03 2015-12 0142-9612 https://pubs.kist.re.kr/handle/201004/124699 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. (C) 2015 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD DOPAMINERGIC-NEURONS HUMAN FIBROBLASTS DIRECT CONVERSION STEM-CELLS MOUSE LMX1A Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system Article 10.1016/j.biomaterials.2015.09.002 1 BIOMATERIALS, v.72, pp.152 - 162 BIOMATERIALS 72 152 162 scie scopus 000362926600014 2-s2.0-84943245228 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article DOPAMINERGIC-NEURONS HUMAN FIBROBLASTS DIRECT CONVERSION STEM-CELLS MOUSE LMX1A Direct lineage reprogramming Gene expression system Induced neurons