Dnmt3a regulates both cell proliferation and differentiation of mouse neural stem cells

DNA methylation is known to regulate cell differentiation and neuronal function in vivo. Here we examined whether deficiency of a de novo DNA methyltransferase, Dnmt3a, affects in vitro differentiation of mouse embryonic stem cells (mESCs) to neuronal and glial cell lineages. We found that Dnmt3a-/- neural stem cells (NSCs) derived from mESCs have globally reduced methylcytosine levels and precociously differentiates into astrocytes and oligodendrocytes, consistent with our previous findings in the more severely hypomethylated Dnmt1-/- NSCs. Moreover, Dnmt3a-/- NSC proliferation rate was significantly increased when compared to control. Thus, our work revealed a novel role for Dnmt3a in regulating both timing of neural cell differentiation and cell proliferation in NSCs. Dnmt3a KO vs. WT neural stem cells; 3 biological replicates of each.