| Autor: |
Santini, Laura, Kowald, Saskia, Cerron-Alvan, Luis Miguel, Huth, Michelle, Fabing, Anna Philina, Sestini, Giovanni, Rivron, Nicolas, Leeb, Martin |
| Předmět: |
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| Zdroj: |
Nature Communications; 9/9/2024, Vol. 15 Issue 1, p1-17, 17p |
| Abstrakt: |
Naïve pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naïve pluripotency-specific transcription factors (TFs). Upon exiting naïve 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 naïve 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 naïve ESCs. PTEN-mediated reduction of AKT activity upon exit from naïve 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. While the core regulators involved in maintenance of naïve and formative pluripotency have been described, less is known about the regulation of the transition between the two states. Here they show that FoxO transcription factors mediate the naïve to formative pluripotency transition and are regulated via AKT phosphorylation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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