Year 3

The overall goal of this project is to understand how STAT3 regulates the fate of mouse and human embryonic stem cells. In the past reporting period, we made the following major advancements:
1. The discovery that activation of STAT3 through phosphorylation at Tyrosine 705 can promote the conversion of mouse epiblast stem cells into a naïve embryonic stem cell state when Serine 727 phosphorylation of STAT3 is simultaneously blocked.
2. Identification of Gbx2 and En2 as the STAT3 downstream targets that play a critical role in sustaining mouse embryonic stem cell self-renewal.
3. Development of a small-molecule based culture condition that can maintain mouse epiblast stem cell and human embryonic stem cell self-renewal.
Our findings suggest that human embryonic stem cells share defined features with mouse epiblast stem cells, but not with mouse embryonic stem cells. Based on these findings, we plan to investigate whether STAT3 regulates the fate of embryonic stem cells and epiblast stem cells through distinct mechanisms.