Int J Stem Cells.  2019 Nov;12(3):474-483. 10.15283/ijsc19075.

Direct Reprogramming to Human Induced Neuronal Progenitors from Fibroblasts of Familial and Sporadic Parkinson’s Disease Patients

Affiliations
  • 1Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea. janghwan.kim@kribb.re.kr, myson@kribb.re.kr
  • 2Department of Functional Genomics, KRIBB, School of Bioscience, University of Science and Technology, Daejeon, Korea.

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

Reprogramming; Direct reprogramming; Induced neuronal progenitor cells; Pluripotency factors; Parkinson’s disease

MeSH Terms

Cell Line
Dopaminergic Neurons
Fibroblasts*
Humans*
In Vitro Techniques
Induced Pluripotent Stem Cells
Karyotype
Neuroblastoma
Neurons*
Pathology
Sendai virus
Stem Cells
Tissue Donors
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