Direct reprogramming to human induced neuronal progenitors from fibroblasts of familial and sporadic Parkinson’s disease patients

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Title
Direct reprogramming to human induced neuronal progenitors from fibroblasts of familial and sporadic Parkinson’s disease patients
Author(s)
Minhyung Lee; Hyuna Sim; Hyunjun Ahn; Jeongmin Ha; Areum BaekYoung Joo JeonMi Young SonJanghwan Kim
Bibliographic Citation
International Journal of Stem Cells, vol. 12, no. 3, pp. 474-483
Publication Year
2019
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.
Keyword
Direct reprogrammingInduced neuronal progenitor cellsParkinson's diseasePluripotency factorsReprogramming
ISSN
2005-3606
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.15283/ijsc19075
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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