miR-124-and let-7-Mediated Reprogram of Human Fibroblasts into SST Interneurons

Many neurological disorders stem from defects in or the loss of specific neurons. Dysfunction of gamma-aminobutyric acid (GABA)ergic interneurons may cause a variety of neurological and psychiatric disorders such as epilepsy, autism, Alzheimer's disease, and depression. Unlike other types of neurons, which can be generated relatively easily by direct reprogramming, it is difficult to generate GABAergic neurons by traditional methods. Neuronal transdifferentiation of fibroblasts mediated by nongenomic-integrated adenovirus has many advantages, but the efficiency is low, and there is a lack of studies using human cells as the initial materials. In this study, we explored the feasibility of the conversion of human fibroblasts into neurons through adenovirus-mediated gene expression and found that by introducing two microRNAs, miR-124 and let-7, together with several small chemical compounds, they can effectively generate GABAergic neuron-like cells from human neonatal fibroblasts without reverting to a progenitor cell stage. Most of these cells expressed neuronal markers and were all somatostatin (SST)-positive cells. Therefore, our study provides a relatively safe and efficient method to generate SST interneurons.