Figure 1.

Capture of a Stem Cell State by Suspending Developmental Progression

A generic scheme illustrating the idea that self-renewal can ensue if the core transcription factor (TF) network is insulated from differentiation cues and requisite metabolic conditions are satisfied. In the specific case of the mouse ESC ground state, the 2i inhibitors block FGF/Erk and Tcf3 differentiation pathways, while LIF boosts the core TF network and also promotes metabolic activity, as does GSK3 inhibition. In the absence of 2i/LIF components, the ESC gene regulatory circuitry collapses and cells transition toward lineage priming and differentiation.