Regulation of neural stem cell self-renewal, proliferation and differentiation by the RhoA guanine nucleotide exchange factor Arhgef 1

Abstract

The role of the Arhgef1 as a RhoA-specific guanine nucleotide exchange factor has been widely investigated in the immune system. Our previous findings reveal that Arhgef 1 is highly expressed in neural stem cells (NSCs) and controls the process of neurite formation. However, the functional role of Arhgef 1 in NSCs remains poorly understood. In order to investigate the role of Arhgef 1 in NSCs, Arhgef 1 expression in NSCs was reduced by using lentivirus-mediated short hairpin RNA interference. Our results indicate that down-regulated expression of Arhgef 1 reduced the self-renewal, proliferation capacity of NSCs and affect cell fate determination. In addition, the comparative transcriptome analysis from RNA-seq data determines the mechanisms of deficits in Arhgef 1 knockdown NSCs. Altogether, our present studies show that Arhgef 1 down-regulation leads to interruption of the cell cycle procession. The importance of Arhgef 1 for regulating self-renewal, proliferation and differentiation in NSCs is reported for the first time.