Role of microRNA-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 this study, microRNA-146 overexpression and predicted target (notch 1) were used to study proliferation and differentiation of mouse NSCs. Short hairpin (sh)-RNA 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'untranslated region 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.