mESC Pluripotency Research Articles

β-catenin does not show nuclear location in undifferentiated murine embryonic stem cells

Murine embryonic stem cells (mESCs) indefinitely proliferate in culture in the presence of LIF and serum growth factors. Signaling pathways governing mESC self-renewal has not been completely understood and require further detailed study. Recently, it was reported that 6-bromoindirubine-3-oxime (BIO), an inhibitor of GSK3 β kinase and activator of Wnt signaling, supports pluripotency of mESCs [11]. β -Catenin is a key effector of the Wnt pathway, which interacts with cadherins and β -catenin, thereby connecting the cell adhesion molecules to the actin-based cytoskeleton. It is a coactivator of transcription together with LEF/TCF factors and forms a cytoplasmic complex with APC, Axin and GSK3 β prior to its GSK3 β -dependent phosphorylation and subsequent degradation [2]. The nuclear location of β -catenin is observed in highly proliferating progenitor cells [6, 10] and several types of tumor cells [5, 7, 13]. This work focuses on the study of β -catenin location in rapidly proliferating undifferentiated and retinoic acid (RA)-differentiated mESCs. We also studied the features of epithelial‐mesenchymal transition (EMT) upon RA-induced differentiation, such as the change in transcription of marker genes, reorganization of the actin-based cytoskeleton structure and location of E- and N-cadherins in differentiated and undifferentiated cells. It was shown that retinoic acidinduced differentiation of mESCs was accompanied by the appearance of markers of EMT. Thus, β -catenin does not show nuclear location in highly proliferating mESCs, in contrast to progenitor cells and some types of tumor cells.