β-Catenin in pluripotency: adhering to self-renewal or Wnting to differentiate?

Abstract

β-Catenin is involved both in cadherin-mediated intercellular adhesion and transcriptional coactivation downstream of the Wnt signaling pathway. Accumulation of β-catenin by inhibition or knockout of its negative regulator GSK3 is known to sustain pluripotency in conjunction with other factors. However, dual function of β-catenin and context-dependence of its activities make it difficult to dissect the mechanisms underlying this phenomenon. β-Catenin transactivation function, which is considered to be associated with Wnt signaling, proved to be largely dispensable for the self-renewal of naïve embryonic stem cells, but required for differentiation. Instead, β-catenin-mediated adhesion is beneficial for self-renewal, though presumably its main role is to stabilize LIF/STAT3 pathway rather than to maintain intercellular contacts per se. Yet recent report implicates E-cadherin-independent cytoplasm activity of β-catenin in pluripotency maintenance. This review focuses on the new data concerning adhesion- and transcription-related activities of β-catenin in control of self-renewal versus differentiation in pluripotent stem cells, as well as analyzing binding partners of β-catenin in embryonic stem cells, which include key pluripotency regulators.