Cell-cell adhesions in embryonic stem cells regulate the stability and transcriptional activity of β-catenin.

E-cadherin (CDH1) is involved in maintaining cell-cell adhesions in embryonic stem cells (ESCs). However, its function in the context of cell fate decisions is largely unknown. Using mouse ESCs (mESCs), we demonstrate that E-cadherin and β-catenin interact at the membrane and continue to do so upon internalization within the cell. Cdh1 -/- mESCs failed to form tight colonies, with altered differentiation, marker expression and retention of pluripotency factors during differentiation. Interestingly, Cdh1 -/- mESCs showed dramatically reduced β-catenin levels. Transcriptional profiling of Cdh1 -/- mESCs displayed a significant alteration in the expression of a subset of β-catenin targets in a cell state- and GSK3β-dependent manner. Our findings hint at hitherto unknown roles played by E-cadherin in regulating the activity of β-catenin in ESCs.