FGF2 supports NANOG expression via pyruvate dehydrogenase-dependent histone acetylation under low oxygen conditions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082255" target="_blank" >RIV/00159816:_____/25:00082255 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00142808

Result on the web

<a href="https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1623814/full" target="_blank" >https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1623814/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcell.2025.1623814" target="_blank" >10.3389/fcell.2025.1623814</a>

Result language

angličtina

Original language name

FGF2 supports NANOG expression via pyruvate dehydrogenase-dependent histone acetylation under low oxygen conditions

Original language description

Introduction The safe and effective application of human pluripotent stem cells (hPSCs) in research and regenerative medicine requires precise control over pluripotency and cell fate. Pluripotency is characterized by high histone acetylation and aerobic glycolysis, while differentiation involves metabolic remodeling and reduced acetylation. Pyruvate dehydrogenase (PDH) links these processes by converting glycolytic pyruvate into acetyl coenzyme A (Ac-CoA), the key substrate for histone acetylation.Methods We investigated how PDH activity regulates histone acetylation and pluripotency maintenance under physiologically relevant oxygen levels (5% and 21% O-2). PDH contribution to histone acetylation was assessed using a specific PDH inhibitor, followed by rescue experiments with acetyl-CoA precursors. hPSCs were exposed to variations in FGF2 signaling and reactive oxygen species (ROS) using H2O2 treatment to evaluate redox-dependent modulation of PDH and downstream effects on pluripotency factors. Protein levels and post-translational modifications were analyzed by Western blotting and quantitative PCR, relative metabolite concentrations by LC-MS, and ROS levels by fluorescence microscopy.Results Active PDH promoted global histone H3 acetylation and upregulated the expression of the pluripotency factor NANOG, specifically under 5% O-2. Mechanistic analysis revealed a novel FGF2-MEK1/2-ERK1/2-ROS signaling axis that regulates PDH activity through redox-sensitive mechanisms. This regulatory pathway was oxygen-dependent and absent under atmospheric oxygen levels (21% O-2).Discussion These findings identify PDH as a redox-sensitive metabolic switch connecting cellular metabolism with the epigenetic control of pluripotency by modulating Ac-CoA availability.Conclusion Our study highlights the importance of oxygen tension, ROS homeostasis, and growth factor signaling in shaping the metabolic-epigenetic landscape of hPSCs, with implications for optimizing stem cell culture and differentiation protocols.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

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Volume of the periodical

13

Issue of the periodical within the volume

Oct 2025

Country of publishing house

CH - SWITZERLAND

Number of pages

21

Pages from-to

1623814

UT code for WoS article

001611202600001

EID of the result in the Scopus database

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