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

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 (P-iPSCs) generated by non-viral methods, into m...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3899054?pdf=render
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author 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
author_facet 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
author_sort Yoo-Wook Kwon
collection DOAJ
description 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 (P-iPSCs) 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.
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spelling doaj.art-fdd24205a478423f87b2ea096e4c251c2022-12-21T17:48:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8573610.1371/journal.pone.0085736Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.Yoo-Wook KwonYeon-Ju ChungJoonoh KimHo-Jae LeeJihwan ParkTae-Young RohHyun-Jai ChoChang-Hwan YoonBon-Kwon KooHyo-Soo KimIn 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 (P-iPSCs) 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.http://europepmc.org/articles/PMC3899054?pdf=render
spellingShingle 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
Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
PLoS ONE
title Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
title_full Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
title_fullStr Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
title_full_unstemmed Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
title_short Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
title_sort comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein based induced pluripotent stem cell
url http://europepmc.org/articles/PMC3899054?pdf=render
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