Skip to main content
. Author manuscript; available in PMC: 2014 Dec 1.
Published in final edited form as: Stem Cells. 2013 Dec;31(12):2667–2679. doi: 10.1002/stem.1371

Figure 7. Schematic model of β-catenin-dependent regulation of pluripotency network.

Figure 7

Oct4-Sox2 binding to Oct-Sox composite motifs maintains activity of key regulators of pluripotency. Tcf3 interaction with Oct factors at the same motif is predicted to destabilize this circuit. CHIR-mediated stabilization of β-catenin has opposing actions. Entry of β-catenin into Oct4/Tcf3 complexes abrogates Tcf3 actions thereby promoting pluripotency. However, the production of active canonical Wnt transcriptional complexes engages differentiation targets destabilizing pluripotency. PD03-mediated inhibition of MEK/ERK signaling restores a pluripotency balance blocking the activation of Wnt dependent differentiation genes enabling culture under 2i conditions. Given the role of MEK/ERK signaling downstream of receptor tyrosine kinases in the regulation of the Ets-family of transcriptional regulators, and the enrichment of Ets motifs in predicted cis-regulatory, we propose the combined action of Wnt and RTK signaling in the differentiation of ES cells.