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 γ-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.