Post-replicative initial expression of the cell fate regulator PAX6 during neuroectoderm formation

Human neuroepithelial cells are the earliest neural progenitor cells (NPC) during brain development. The cell cycle is fundamental for cell proliferation and differentiation. How the cell cycle is linked to the differentiation process from embryonic stem cells (ESC) in blastocytes to neuroepithelial cells, however, is still unclear. In this study, using an in vitro ESC-to-NPC differentiation system and PAX6 as an NPC cell fate indicator, we discovered that the neural cell fate was transited, PAX6 expression exhibiting an incremental rise, during the G2 phase. For the mechanism, the loss of -401 bp to -450 bp from the transcription start site (TSS) of PAX6 efficiently blocked the cell cycle-dependent expression of PAX6. In addition, we found that using hydroxyurea to arrest the cell cycle of differentiating NPC could prevent NPC differentiation. Overall, this study reported the first scenario to link cell cycle and cell fate transition during early neurogenesis.