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Updated: Jun 13, 2025
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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
Published on: May 30, 2012
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FoxO transcription factors actuate the formative pluripotency specific gene expression programme
Laura Santini1,2, Saskia Kowald1, Luis Miguel Cerron-Alvan1,2
1Max Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.
Nature Communications
|September 9, 2024
Summary
FoxO transcription factors (TFs) are key to cell fate transitions. They enter the nucleus upon exit from naïve pluripotency, activating formative pluripotency enhancers and establishing a critical early embryonic cell state.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Gene Regulation
Background:
- Naïve pluripotency in embryonic stem cells (ESCs) is maintained by a specific gene regulatory network (GRN).
- Exiting naïve pluripotency involves a transition to a formative state, enabling lineage choices, but the underlying mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms controlling the transition from naïve to formative pluripotency.
- To identify the key factors involved in initiating the formative GRN.
Main Methods:
- Investigated the role of AKT signaling and FoxO transcription factors (TFs) in ESCs.
- Analyzed TF localization and enhancer binding during pluripotency exit.
- Assessed the necessity and sufficiency of FoxO TFs in activating the formative GRN.
Main Results:
- Phosphorylated AKT acts as a gatekeeper, inhibiting FoxO TF nuclear localization in naïve ESCs.
- Reduced AKT activity upon exiting naïve pluripotency permits FoxO TF nuclear entry.
- FoxO TFs bind and activate formative pluripotency-specific enhancers, driving cell fate transition.
Conclusions:
- FoxO TFs are essential and sufficient for activating the formative pluripotency GRN.
- The AKT/PTEN/FoxO axis plays a pivotal role in establishing formative pluripotency.
- This study uncovers a critical mechanism for early embryonic cell fate determination.
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