FIGURE 2.

Schematic of the conversion of naïve embryonic stem cells (ESCs) to primed ESCs. The “downstream” pathway follows a normal developmental program and tends to be relatively easy and efficient. The reverse process, reverting primed cells to naïve cells, is arguably an artificial process and consequently more difficult and inefficient. Epigenetic barriers exist between the primed and naïve cells, and there may be more than one way to proceed through these epigenetic barriers. The many epigenetic barriers and the divergent pathways have likely contributed to the difficulty in generating human naïve ESCs. In addition to the naïve and primed states, there is also a formative state that exists intermediate to naïve and primed cells but is capable of primordial germ cell (PGC) formation.