title: Transfection of arginine decarboxylase gene increases the neuronal differentiation of neural progenitor cells.
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.
authors: Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; CSIR-Centre for Cellular and Molecular Biology, Medical Biotechnology Complex, ANNEXE II, Uppal Road, Uppal, Hyderabad 500007, India. Electronic address: bokarakiran@gmail.com.
authors: Kiran Kumar
authors: KK
authors: Bokara
authors: Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea; Department of Biomedical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea. Electronic address: jhkim74@skku.edu.
authors: Jae Hwan
authors: JH
authors: Kim
authors: Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: jykim13@yuhs.ac.
authors: Jae Young
authors: JY
authors: Kim
authors: Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; BK 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: jelee@yuhs.ac.
authors: Jong Eun
authors: JE
authors: Lee
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D019208:Brain-Derived Neurotrophic Factor; D034741:RNA, Small Interfering; D051785:Smad Proteins; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002262:Carboxy-Lyases; C019722:arginine decarboxylase
keywords: Arginine decarboxylase; Neural progenitor cells; Neuronal differentiation