The intracellular relocation of the DNMTs was also associated with differentiation. The nuclear DNMTs prevailed in the undifferentiated state of NSCs, while cytoplasmic DNMTs were dominant in differentiating NSCs. This is consistent with the compartmentalization of the 5-MeC from the nucleus to the perinucleus. This relocation may have effects on remodeling of the heterochromatin state in NSCs. A clear support of this finding comes from bright-field microscopy double registration, which demonstrated that those migrated cells containing bright nuclear 5-MeC were not well differentiated, but the migrated NSCs containing dim and perinuclear 5-MeC were well differentiated with neural fiber extensions (Figure 4). These translocations of 5-MeC and DNMT transition along the differentiation profile are the first report of this kind, which is critical for understanding epigenetic regulation of neural stem cells differentiation, and warrants further investigation of its associated genes.
