| First Author | Santini L | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 7879 |
| PubMed ID | 39251582 | Mgi Jnum | J:354185 |
| Mgi Id | MGI:7732352 | Doi | 10.1038/s41467-024-51794-9 |
| Citation | Santini L, et al. (2024) FoxO transcription factors actuate the formative pluripotency specific gene expression programme. Nat Commun 15(1):7879 |
| abstractText | Naive pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naive pluripotency-specific transcription factors (TFs). Upon exiting naive pluripotency, embryonic stem cells (ESCs) transition through a formative post-implantation-like pluripotent state, where they acquire competence for lineage choice. However, the mechanisms underlying disengagement from the naive GRN and initiation of the formative GRN are unclear. Here, we demonstrate that phosphorylated AKT acts as a gatekeeper that prevents nuclear localisation of FoxO TFs in naive ESCs. PTEN-mediated reduction of AKT activity upon exit from naive pluripotency allows nuclear entry of FoxO TFs, enforcing a cell fate transition by binding and activating formative pluripotency-specific enhancers. Indeed, FoxO TFs are necessary and sufficient for the activation of the formative pluripotency-specific GRN. Our work uncovers a pivotal role for FoxO TFs in establishing formative post-implantation pluripotency, a critical early embryonic cell fate transition. |
