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Direct Reprogramming to Human Induced Neuronal Progenitors from Fibroblasts of Familial and Sporadic Parkinson’s Disease Patients
International Journal of Stem Cells
Published online August 31, 2019;  
© 2019 Korean Society for Stem Cell Research.

Minhyung Lee1,2, Hyuna Sim1,2, Hyunjun Ahn1,2, Jeongmin Ha1,2, Aruem Baek1, Young-Joo Jeon1, Mi-Young Son1,2, Janghwan Kim1,2

1Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
2Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon, Korea
Correspondence to: Janghwan Kim
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
Tel: +82-42-860-4478, Fax: +82-42-860-4608
E-mail: janghwan.kim@kribb.re.kr
Co-Correspondence to: Mi-Young Son
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
Tel: +82-42-860-4426, Fax: +82-42-860-4608
E-mail: myson@kribb.re.kr
Received June 7, 2019; Revised June 20, 2019; Accepted June 21, 2019.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
In Parkinson’s disease (PD) research, human neuroblastoma and immortalized neural cell lines have been widely used as in vitro models. The advancement in the field of reprogramming technology has provided tools for generating patient- specific induced pluripotent stem cells (hiPSCs) as well as human induced neuronal progenitor cells (hiNPCs). These cells have revolutionized the field of disease modeling, especially in neural diseases. Although the direct reprogramming to hiNPCs has several advantages over differentiation after hiPSC reprogramming, such as the time required and the simple procedure, relatively few studies have utilized hiNPCs. Here, we optimized the protocol for hiNPC reprogramming using pluripotency factors and Sendai virus. In addition, we generated hiNPCs of two healthy donors, a sporadic PD patient, and a familial patient with the LRRK2 G2019S mutation (L2GS). The four hiNPC cell lines are highly proliferative, expressed NPC markers, maintained the normal karyotype, and have the differentiation potential of dopaminergic neurons. Importantly, the patient hiNPCs show different apoptotic marker expression. Thus, these hiNPCs, in addition to hiPSCs, are a favorable option to study PD pathology.
Keywords : Reprogramming, Direct reprogramming, Induced neuronal progenitor cells, Pluripotency factors, Parkinson’s disease