Abstract

As cells divide, they must replicate both their DNA and generate a new set of histone proteins. The newly synthesized daughter strands and histones are unmodified and must therefore be covalently modified to allow for transmission of important epigenetic marks to daughter cells. Human pluripotent stem cells (hPSCs) display a unique cell cycle profile, and control of the cell cycle is known to be critical for their proper differentiation and survival. A major unresolved question is how hPSCs regulate their DNA methylation status through the cell cycle, namely how passive and active demethylation work to maintain a stable genome. TDG, an embryonic essential gene, has been recently implicated as a major enzyme involved in demethylation1. Here we present new data showing that TDG regulates cell cycle related gene expression in human neural progenitors (NPCs) derived from hPSCs and controls their capacity for neural differentiation. These observations suggest that TDG and active demethylation play an important role in hPSC cell cycle regulation and differentiation.