title: Neurogenin 2 enhances the neuronal differentiation of skin-derived precursors.
abstract: Skin-derived precursors (SKPs), a novel stem cell population isolated from mammalian skin, can differentiate into neural and mesodermal lineages. Cell therapy using SKPs seems like a promising approach for the treatment of neural diseases, however, the low efficiency of neuronal differentiation limited their clinical application. In the present study, we transfected neurogenin 2 (Ngn2), a member of the bHLH transcription factor family, into SKPs by lentivirus. Morphological analysis, immunocytochemistry, Western blot, and electrophysiological analysis were performed to identify the cells derived from SKPs following 7-14 d neural induction. The results of immunocytochemistry staining showed that expression of neuronal markers, including MAP2, NF and NeuN were significantly elevated compared with those in GFP-SKPs and parental SKPs. Western blot confirmed the increased expression of NF-M and NeuN in Ngn2-SKPs-derived cells. Moreover, electrophysiological analysis showed that Ngn2-SKPs-derived neurons also acquired voltage-gated Na+ channels, which were absent in GFP-SKPs. Furthermore, western blot showed that Ngn2 enhanced the expression of Delta-like1, which reduced the level of Hes1 and suppressed Notch pathway. Therefore, overexpression of Ngn2 enhanced the neural differentiation of SKPs, probably through cis-inhibiting of Notch signal pathway.
authors.affiliation: 1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, China.
authors.forename: XueLiang
authors.initials: X
authors.lastname: Dai
authors.forename: XiaoCheng
authors.initials: X
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: HuaiYong
authors.initials: H
authors.lastname: Hao
authors.forename: TengDa
authors.initials: T
authors.lastname: Qian
authors.forename: Wan
authors.initials: W
authors.lastname: Yu
authors.forename: LinJun
authors.initials: L
authors.lastname: Tang
authors.forename: LiXin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C534807:Neurog2 protein, rat
keywords: Notch signal pathway; neural differentiation; neurogenin2; skin-derived precursors