title: Mesenchymal stem cells regulate the proliferation and differentiation of neural stem cells through Notch signaling.
abstract: The effects of mesenchymal stem cells (MSCs) on proliferation and cell fate determination of neural stem cells (NSCs) have been investigated. NSCs were co-cultured with MSCs or NIH3T3 cells using an in vitro transwell system. After 4 days, immunofluorescence staining showed that the number of cells positive for the cell proliferation antigen, ki-67, in neurospheres in MSCs was greater than in NIH3T3 cells. In some experiments, the top-layers of MSCs and NIH3T3 cells were removed to induce NSCs differentiation. Seven days after initiating differentiation, the levels of the neuronal marker, NSE, were higher in NSCs in MSCs co-culture group, and those of glial fibrillary acidic protein (GFAP) were lower, compared with NIH3T3 cells co-culture group. These were confirmed by immunofluorescence. The role of the Notch signaling pathway analyzed with the specific inhibitor, DAPT, and by examining the expression of Notch-related genes using RT-PCR showed that after co-culturing with MSCs for 24h, NSCs expressed much higher levels of ki-67, Notch1, and Hes1 than did NSCs co-cultured with NIH3T3 cells. Treatment with DAPT decreased ki-67, Notch1 and Hes1 expression in NCSs, and increased Mash1 expression. The data indicate that the interactions between MSCs and NSCs promote NSCs proliferation and are involved in specifying neuronal fate, mediated in part by Notch signaling.
authors.affiliation: Institute of Urology, Nanchang University, Nanchang 330006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.forename: Yuanlei
authors.initials: Y
authors.lastname: Lou
authors.forename: An
authors.initials: A
authors.lastname: Xie
authors.forename: Xianliang
authors.initials: X
authors.lastname: Lai
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Deng
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D018398:Homeodomain Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D019899:Paracrine Communication; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C499317:Ascl1 protein, mouse; C489734:Hes1 protein, mouse