Figure 6.

Proposed model of processes occurring during the differentiation of ESCs to EpiSCs. ESC cultures contain a small fraction of Oct4-negative cells and a rare subpopulation of these cells expresses Cdx2. During the differentiation of ESCs to EpiSCs, the differentiating ESCs downregulate Oct4 and undergo a temporary cell cycle arrest. The Oct4-negative Cdx2-positive cells are unaffected by the culture conditions and continue to proliferate leading to a temporary enrichment of these cells within the population. The cells that are not competent to undergo differentiation are eliminated by apoptosis. As the differentiation competent ESCs acquire EpiSC identity, they have reacquired Oct4 expression and proliferative ability and overtake the culture. These processes occurring during ESC to EpiSC differentiation were clearly unmasked in the ShcD−/− cells as they were enhanced and prolonged prior to the recovery and acquisition of EpiSC state. Abbreviations: EpiSC, epiblast stem cell; ESC, embryonic stem cell.