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

Hanseul Park, Hongwon Kim, Junsang Yoo, Jaekwang Lee, Hwan Choi, Soonbong Baek, C. Justin Lee, Janghwan Kim, Christopher J. Lengner, Jung Suk Sung, Jongpil Kim

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)152-162
Number of pages11
JournalBiomaterials
Volume72
DOIs
Publication statusPublished - 2015 Dec

Keywords

  • Direct lineage reprogramming
  • Gene expression system
  • Induced neurons

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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