Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell

Yoo Wook Kwon, Yeon Ju Chung, Joonoh Kim, Ho Jae Lee, Jihwan Park, Tae Young Roh, Hyun Jai Cho, Chang Hwan Yoon, Bon Kwon Koo, Hyo Soo Kim

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

In patients with Parkinson's disease (PD), stem cells can serve as therapeutic agents to restore or regenerate injured nervous system. Here, we differentiated two types of stem cells; mouse embryonic stem cells (mESCs) and protein-based iPS cells (PiPSCs) generated by non-viral methods, into midbrain dopaminergic (mDA) neurons, and then compared the efficiency of DA neuron differentiation from these two cell types. In the undifferentiated stage, P-iPSCs expressed pluripotency markers as ES cells did, indicating that protein-based reprogramming was stable and authentic. While both stem cell types were differentiated to the terminally-matured mDA neurons, P-iPSCs showed higher DA neuron-specific markers' expression than ES cells. To investigate the mechanism of the superior induction capacity of DA neurons observed in P-iPSCs compared to ES cells, we analyzed histone modifications by genome-wide ChIP sequencing analysis and their corresponding microarray results between two cell types. We found that Wnt signaling was up-regulated, while SFRP1, a counter-acting molecule of Wnt, was more suppressed in P-iPSCs than in mESCs. In PD rat model, transplantation of neural precursor cells derived from both cell types showed improved function. The present study demonstrates that P-iPSCs could be a suitable cell source to provide patient-specific therapy for PD without ethical problems or rejection issues.

Original languageEnglish
Article numbere85736
JournalPLoS ONE
Volume9
Issue number1
DOIs
StatePublished - 22 Jan 2014

Fingerprint

Dive into the research topics of 'Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell'. Together they form a unique fingerprint.

Cite this