| First Author | Wray J | Year | 2011 |
| Journal | Nat Cell Biol | Volume | 13 |
| Issue | 7 | Pages | 838-45 |
| PubMed ID | 21685889 | Mgi Jnum | J:174453 |
| Mgi Id | MGI:5086054 | Doi | 10.1038/ncb2267 |
| Citation | Wray J, et al. (2011) Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation. Nat Cell Biol 13(7):838-45 |
| abstractText | Self-renewal of rodent embryonic stem cells is enhanced by partial inhibition of glycogen synthase kinase-3 (Gsk3; refs , ). This effect has variously been attributed to stimulation of Wnt signalling by beta-catenin, stabilization of Myc protein and global de-inhibition of anabolic processes. Here we demonstrate that beta-catenin is not necessary for embryonic stem cell identity or expansion, but its absence eliminates the self-renewal response to Gsk3 inhibition. Responsiveness is fully restored by truncated beta-catenin lacking the carboxy-terminal transactivation domain. However, requirement for Gsk3 inhibition is dictated by expression of T-cell factor 3 (Tcf3) and mediated by direct interaction with beta-catenin. Tcf3 localizes to many pluripotency genes in embryonic stem cells. Our findings confirm that Tcf3 acts as a transcriptional repressor and reveal that beta-catenin directly abrogates Tcf3 function. We conclude that Gsk3 inhibition stabilizes the embryonic stem cell state primarily by reducing repressive influence on the core pluripotency network. |
