Year 5

The overall goal of this project was to understand how STAT3 regulates the fate of mouse and human embryonic stem cells. In the past reporting period, we found that knockdown of Crif1, a protein associated with STAT3, impairs mouse embryonic stem cell self-renewal mediated by LIF/STAT3 signaling. We also identified and characterized two genes that are regulated by LIF/STAT3 signaling and involved in regulating embryonic stem cell fate. The first is Lef1. We found that Lef1 is negatively regulated by LIF/STAT3 signaling and knockdown of Lef1 promotes mouse embryonic stem cell self-renewal. The other gene is Cdx2 which is induced when STAT3 is hyperactivated. Induction of Cdx2 induces trophoblast differentiation of mouse embryonic stem cells. These findings provide an expanded understanding of embryonic stem cell fate regulation and are important for the future of cell replacement therapy using cells derived from embryonic stem cells.