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Transfection of arginine decarboxylase gene increases the neuronal differentiation of neural progenitor cells

Authors
 Kiran Kumar Bokara  ;  Jae Hwan Kim  ;  Jae Young Kim  ;  Jong Eun Lee 
Citation
 STEM CELL RESEARCH, Vol.17(2) : 256-265, 2016 
Journal Title
STEM CELL RESEARCH
ISSN
 1873-5061 
Issue Date
2016
Keywords
Animals ; Bone Morphogenetic Proteins/metabolism ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Carboxy-Lyases/antagonists & inhibitors ; Carboxy-Lyases/genetics ; Carboxy-Lyases/metabolism* ; Cell Differentiation ; Cells, Cultured ; Female ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Mice ; Mice, Inbred ICR ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism* ; Neurogenesis ; Phosphatidylinositol 3-Kinases/metabolism ; Plasmids/genetics ; Plasmids/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Smad Proteins/metabolism ; Wnt Signaling Pathway
Abstract
Growing evidence suggests that the clinical use of neural progenitor cells (NPCs) is hampered by heterogeneity, poor neuronal yield and low survival rate. Recently, we reported that retrovirus-delivered human arginine decarboxylase (hADC) genes improve cell survival against oxidative insult in murine NPCs in vitro. This study investigates whether the induced expression of hADC gene in mNPCs induces any significant change in the cell fate commitment. The evaluation of induced hADC gene function was assessed by knockdown of hADC gene using specific siRNA. The hADC gene delivery triggered higher expression of N-CAM, cell adhesion molecule and MAP-2, neuronal marker. However, the hADC gene knockdown showed downregulation of N-CAM and MAP-2 expression suggesting that hADC gene delivery favors cell fate commitment of mNPCs towards neuronal lineage. Neurite outgrowth was significantly longer in the hADC infected cells. The neurotrophic signal, BDNF aided in the neuronal commitment, differentiation, and maturation of hADC-mNPCs through PI3K and ERK1/2 activation. The induction of neuron-like differentiation is believed to be regulated by the expression of GSK-3β and Wnt/β-catenin signaling pathways. Our findings suggest that hADC gene delivery favors cell fate commitment of mNPCs towards neuronal lineage, bring new advances in the field of neurogenesis and cell therapy.
Files in This Item:
T201603288.pdf Download
DOI
10.1016/j.scr.2016.08.009
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Young(김재영)
Kim, Jae Hwan(김재환)
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151969
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