| First Author | Ye S | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 19 | Pages | 2548-60 |
| PubMed ID | 23942238 | Mgi Jnum | J:202487 |
| Mgi Id | MGI:5519176 | Doi | 10.1038/emboj.2013.175 |
| Citation | Ye S, et al. (2013) Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1. EMBO J 32(19):2548-60 |
| abstractText | Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naive pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. |
