Evidence map›Paper›PMID 39251582›Full record

ArticleNature communications2024

FoxO transcription factors actuate the formative pluripotency specific gene expression programme.

Laura Santini, Saskia Kowald, Luis Miguel Cerron-Alvan, Michelle Huth, Anna Philina Fabing, Giovanni Sestini, Nicolas Rivron, Martin Leeb

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Review
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  9. Review
  10. PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Laura SantiniMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.ORCID 0000-0001-9968-2459
Saskia KowaldMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.
Luis Miguel Cerron-AlvanMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.
Michelle HuthMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.ORCID 0000-0002-1152-9140
Anna Philina FabingMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.
Giovanni SestiniVienna BioCenter PhD Program, Doctoral School of the University of Vienna, Medical University of Vienna, 1030, Vienna, Austria.ORCID 0000-0002-6643-7585
Nicolas RivronInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, 1030, Vienna, Austria.ORCID 0000-0003-1590-5964
Martin LeebMax Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria. martin.leeb@univie.ac.at.ORCID 0000-0001-5114-4782

Funding

Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) I 5958Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) W 1261Austrian Science Fund FWF DOC 72Österreichischen Akademie der Wissenschaften (Austrian Academy of Sciences) DOC/25622Vienna Science and Technology Fund (Wiener Wissenschafts-, Forschungs- und Technologiefonds) VRG14-006
6 · The paper itself

Abstract

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.

Indexed as

Gene Regulatory NetworksPluripotent Stem CellsAnimalsCell DifferentiationEmbryonic Stem CellsForkhead Box Protein O1Forkhead Transcription FactorsGene Expression Regulation, DevelopmentalMiceMouse Embryonic Stem CellsPhosphorylationProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseForkhead Box Protein O1Forkhead Transcription FactorsFoxo1 protein, mouseProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePten protein, mouse

Identifiers

PMID39251582
PMCPMC11384738

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.