The Determinant Role of miR-19 in Neural Stem Cell Fate: The Red Light to the Neuronal Differentiation and the Green Light to the Oligodendrocyte Differentiation

Abstract Background The precise epigenetic pathways and mechanisms involved in determining the fate of neural progenitor stem cells (NPCs) into differentiated neural lineages including oligodendrocytes (OLs) is an unresolved issue. MiRNAs are one of the key differentiating factors whose aberrant expression has been shown to disturb proper development. In the present study the leading role of miR-19 in NPCs differentiation to OLs was investigated.Methods MiR-19 was overexpressed in hiPSC derived NPCs and for confirming differentiation to the desired cell line, i.e. OL, the expression of cell line-specific genes was evaluated by Real-Time PCR. Oligodendrocyte progenitor cells (OPCs) precursor in the differentiated cells was studied by Flow cytometry. Luciferase activity was also measured to confirm the interaction of miR-19 with the 3’UTR of mRNA of the putative genes. Results Our results indicate that the upregulation of miR-19 is a contributing factor in determining NPCs' fate and the timing of progenitor division arrest. MiR-19 can cause a significant expression of OL markers. Besides, miR-19 repressed proneuronal differentiation factors including NeuroD1, NeuroD4, and neurogenin. Moreover, the higher expression of miR-19 could downregulate SOX4, SOX5, and SOX6 genes, which are involved in inhibiting OL differentiation and maturation. Conclusions Our finding demonstrated the functional link of miR-19 to regulatory networks of NPCs differentiation, as well as introduced a new strategy for modulating OL fate commitment and development of novel cell therapies.