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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00142808

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

Oct 2025

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

21

Strana od-do

1623814

Kód UT WoS článku

001611202600001

EID výsledku v databázi Scopus

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