Critical role of Tet3 in neural progenitor cell maintenance and terminal differentiation.

5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem cells (ESCs) and in the brain. However, the role of 5hmC and Tet family in the process of ESC differentiation especially neuronal differentiation remains elusive. Here, we showed the evidence that Tet3 is critical in neural progenitor cell (NPC) maintenance and terminal differentiation of neurons. We found that Tet3 expression is basically undetectable in ESCs, but its level increases rapidly during neuronal differentiation. Tet3 knockout ESCs appear normal in self-renewal and maintenance but impaired in neuronal differentiation. NPCs could be induced efficiently from Tet3 knockout ESCs, as the expression of NPC marker Pax6 and nestin is comparable with NPCs from wild-type ESCs, but undergo apoptosis rapidly, and the terminal differentiation of neurons is greatly reduced. Our results indicate that Tet3 is important for NPC maintenance and terminal differentiation of neurons.