MiR-223 regulates the differentiation of immature neurons

Abstract

BACKGROUND Small non-coding microRNA RNA molecules can regulate stem cell function. The role of microRNAs in neural stem/progenitor cells (NS/PCs) differentiation is not entirely clear. METHODS MiRNA profiling, loss and gain of function studies coupled with dendritic tree development morphometric analysis and calcium influx imaging were utilized to investigate the role of micoRNA-223 in differentiating NS/PCs. RESULTS MiRNA profiling in human NS/PCs before and after differentiation in vitro reveals modulation of miRNAs following differentiation of NS/PCs. MiR-223, a microRNA well characterized as a hematopoietic-specific miRNA was identified. Cell-autonomous inhibition of miR-223 in the adult mouse dentate gyrus NS/PCs led to a significant increase in immature neurons soma size, dendritic tree total length, branch number per neuron and complexity, while neuronal migration in the dentate gyrus remained unaffected. Overexpression of miR-223 decreased dendritic tree total length, branch number and complexity in neurons differentiated from human embryonic stem cells (hESCs). Inhibition of miR-223 enhanced N-methyl-D-aspartate (NMDA) induced calcium influx in human neurons differentiated from NS/PCs. CONCLUSIONS Taken together, these findings indicate that miR-223 regulates the differentiation of neurons derived from NS/PCs.