International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Direct Reprogramming to Human Induced Neuronal Progenitors from Fibroblasts of Familial and Sporadic Parkinson's Disease Patients

  • Lee, Minhyung (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Sim, Hyuna (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ahn, Hyunjun (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ha, Jeongmin (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Baek, Aruem (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jeon, Young-Joo (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Son, Mi-Young (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Janghwan (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2019.06.07
  • Accepted : 2019.06.21
  • Published : 2019.11.30
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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

Acknowledgement

This work was supported by the KRIBB Research Initiative and Stem Cell Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (2013M3A9B4076483, 2015M3A9C7030128, 2018M3A9H3023077, and 2016K1A3A1A61006001) and a grant from Ministry of Food and Drug Safety in 2018 (18172MFDS182).

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