Beta-catenin signaling contributes to stemness and regulates early differentiation in murine embryonic stem cells.

ES cells can self-renew while preserving pluripotency and are able to differentiate into many cell types. In both processes, different signal transduction pathways are implicated, including the Wnt/beta-catenin pathway, which we here further analyzed. We found that a loss of beta-catenin in ES cells leads to altered expression of stem cell marker genes. TCF/beta-catenin reporter gene assays indicate that undifferentiated murine ES cells are capable of reacting to LiCl and Wnt3a but not Wnt5a stimulation, but have low endogenous TCF/beta-catenin activity. Oct-3/4, nanog and Wnt11 were able to repress TCF/beta-catenin transcriptional activity. During differentiation, activation of the Wnt/beta-catenin pathway influences formation of mesoderm and cardiomyocytes in a time and dose dependent manner.