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.