Efficient and rapid generation of neural stem cells by direct conversion of fibroblasts with single microRNAs.

Abstract

Neural stem cells (NSCs) hold great potential in neurodegenerative disease therapy, drug screening, and disease modeling. However, current approaches for induced NSCs (iNSCs) generation from somatic cells are still slow and inefficient. Here we report the establishment of a rapid and efficient method of iNSCs generation from human and mouse fibroblasts by using single microRNAs (miR-302a). These iNSCs exhibited morphological, molecular and functional properties resembling those of adult human and mouse NSCs, respectively. Additionally, human iNSCs can be expanded for more than 20 passages in vitro. Furthermore, miR-302a alone was demonstrated to be sufficient to reprogram both human and mouse fibroblasts into iNSCs. Our results showed a method of direct conversion of autologous fibroblasts with miR-302a into iNSCs, providing a rapid and efficient strategy to generate iNSCs for both basic research and clinical applications.