Efficient and Rapid Generation of Neural Stem Cells by Direct Conversion Fibroblasts with Single microRNAs

Abstract Neural stem cells (NSCs) have great potentials in the application of 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 establish a rapid and efficient method of iNSCs generation from human and mouse fibroblasts by single microRNAs (miR-302a). These iNSCs exhibited morphological, molecular and functional properties resembling those of adult human and mouse NSCs, and 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 that direct conversion of autologous fibroblasts with miR-302a into iNSCs, which provides a rapid and efficient strategy to generate iNSCs for both basic research and clinical applications.