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.
Bibliographical noteFunding Information:
Authors would like to thank Dr. T. Ramakrishna Murti for his valuable comments and linguistic corrections in the manuscript. Authors would also like to thank D.I Biotech (Seoul, Korea) for support to analyze neurite outgrowth. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) ( NRF-2014R1A2A2A01006556 and NRF-2013R1A1A2062711 ), and CSIR network project BSC 0115 (mIND) INDIA ( BSC-0115 ).
All Science Journal Classification (ASJC) codes
- Developmental Biology
- Cell Biology