| First Author | Chatterjee SS | Year | 2015 |
| Journal | J Cell Biol | Volume | 211 |
| Issue | 1 | Pages | 39-51 |
| PubMed ID | 26459597 | Mgi Jnum | J:230593 |
| Mgi Id | MGI:5763335 | Doi | 10.1083/jcb.201503017 |
| Citation | Chatterjee SS, et al. (2015) Inhibition of beta-catenin-TCF1 interaction delays differentiation of mouse embryonic stem cells. J Cell Biol 211(1):39-51 |
| abstractText | The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/beta-catenin pathway promotes pluripotency by alleviating T cell factor TCF3-mediated repression of the PTN. However, it has remained unclear how beta-catenin's function as a transcriptional activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription is up-regulated in differentiating mESCs and that chemical inhibition of beta-catenin/TCF1 interaction improves long-term self-renewal and enhances functional pluripotency. Genetic loss of TCF1 inhibited differentiation by delaying exit from pluripotency and conferred a transcriptional profile strikingly reminiscent of self-renewing mESCs with high Nanog expression. Together, our data suggest that beta-catenin's function in regulating mESCs is highly context specific and that its interaction with TCF1 promotes differentiation, further highlighting the need for understanding how its individual protein-protein interactions drive stem cell fate. |
