Timing of the cell cycle exit of differentiating hippocampal neural stem cells.

Neural stem cells contribute to mammalian brain tissue turnover in specific locations throughout life. Differentiation of stem cells is associated with terminal mitosis and cell cycle exit, but it is unclear how the timing and signaling of these are interlinked. Here, we have investigated the cell cycle exit characteristics in comparison with morphological changes during hippocampal stem cell differentiation in an adult mammalian cell line. Our results suggest that the cell-specific gene pathway induction is fast and robust and takes place in one day, whereas the cell cycle exit machinery is slower and takes several days to fully execute. The hippocampal differentiation is associated with epigenetic changes, such as Ezh2 down regulation and histone methylation. A small percentage of stem cells is able to resist differentiation-induced terminal mitosis for weeks in culture, and can be reverted to proliferation by re-adding the mitotic growth factors.