Background: Stem cells have been extensively found in different tissues and organs. Understanding the characteristics of stem cells to maintain their stability may lead to find new ways to control stem cell differentiation. Methods:In this study, the surface potential variation of neural stem/ progenitor cells (NSPCs) during differentiation process was examined. Using cell electrophoresis for measuring the electrophoretic mobility of NSPCs, we showed the electrophoretic mobility of NSPCs could rapidly increase during the first hour of differentiation process. Moreover, an activation energy model describing the variation of the surface potential of NSPCs was proposed.Findings: When NSPCs need to change their phenotypes to differentiate, they require enough energy to process this phenotype alteration. Thus, NSPC differentiation could be enhanced or delayed by controlling electrophoretic mobility of cells, which provided a new vision for stem cell differentiation. Conclusions:This study provided an alternative to regulate the NSPC differentiation by controlling the cellular electrophoretic mobility.