title: Role of miRNA-146 in proliferation and differentiation of mouse neural stem cells.
abstract: Neural stem cells (NSCs) have been defined as neural cells with the potential to self-renew and eventually generate all cell types of the nervous system. NSCs serve as an ideal cell type for nervous system repair. In the present study, miR-146 overexpression and predicted target (notch 1) were used to study proliferation and differentiation of mouse NSCs. shRNA were used to demonstrate the function of Notch 1 in proliferation of mouse NSCs and luciferase reporter assay was used to assess and confirm the binding sequence of 3'-UTR between Notch 1 and miR-146. Results showed that miR-146 overexpression and knockdown of notch 1 inhibited proliferation of mouse NSCs under serum-free cultural conditions and promoted spontaneous differentiation of mouse NSCs under contained serum cultural conditions respectively. Mouse NSCs spontaneously underwent differentiation into neurogenic cells with contained serum medium. However, when miR-146 was overexpressed, differentiation efficiency of glial cells from NSCs was increased, suggesting that Notch1 promoted NSC proliferation and repressed spontaneous differentiation of NSC in serum-free medium. In conclusion, our results demonstrate that miR-146 promoted spontaneous differentiation of NSCs, and this mechanism was influenced by miR-146, as well as its target (notch 1) and downstream gene.
authors.affiliation: Department of Neurology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China Department of Neurosurgery GanSu Provincial Hospital, LanZhou, GanSu 730000, PR China.
authors.forename: An-Qing
authors.initials: AQ
authors.lastname: Lu
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Shenyang, Liaoning 110016. PR China.
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China No.705 Hospital of Chinese Airforce, Shenyang 110000, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China Department of Emergency, 463rd Hospital of PLA, Shenyang 110042, PR China profyingzi@163.com zhiweiwang001@hotmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zi
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China profyingzi@163.com zhiweiwang001@hotmail.com.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1
keywords: cell proliferation; differentiation; microRNA; neural stem cells