Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells.

Embryonic stem cells (ESCs) can self-renew indefinitely while maintaining the ability to generate all three germ-layer derivatives. Despite the importance of ESCs in developmental biology and their potential impact on regenerative medicine, the molecular mechanisms controlling ESC behavior are incompletely understood. Previously, activation of the canonical Wnt signaling pathway has been shown to contribute to mouse ESC self-renewal. Here we report that ectopic expression of Lef1, a component of the Wnt signaling pathway, has a positive effect on the self-renewal of mouse ESCs. Lef1 up-regulates Oct4 promoter activity and physically interacts with Nanog, two key components of the ESC pluripotency machinery. Moreover, siRNA for Lef1 induced mouse ESC differentiation. Our results thus suggest that in response to Wnt signaling Lef1 binds to stabilized beta-catenin and helps maintain the undifferentiated status of ESCs through modulation of Oct4 and Nanog.