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FGF2-induced Redox Signaling: A Mechanism Regulating Pyruvate Dehydrogenase Driven Histone Acetylation and NANOG Upregulation
FGF2-induced Redox Signaling: A Mechanism Regulating Pyruvate Dehydrogenase Driven Histone Acetylation and NANOG Upregulation
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Length:
20 minutes
Released:
Jan 20, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.01.20.524871v1?rss=1
Authors: Fojtik, P., Senfluk, M., Holomkova, K., Salykin, A., Gregorova, J., Smak, P., Pes, O., Raska, J., Stetkova, M., Skladal, P., Sedlackova, M., Hampl, A., Bohaciakova, D., Uldrijan, S., Rotrekl, V.
Abstract:
Precise control of pluripotency is a requirement for the safe and effective use of hPSCs in research and therapies. Here we report that pyruvate dehydrogenase upregulates histone H3 pan acetylation and levels of pluripotency marker NANOG in 5% O2. Pyruvate dehydrogenase (PDH) is an essential metabolic switch and a bottleneck for the glycolytic production of acetyl-CoA. Silencing of gene expression showed that PDH is regulated by the activity of its phosphatase PDP1. We show that PDP1 is sensitive to reactive oxygen species-mediated inactivation, leading to the downregulation of H3 pan acetylation and NANOG levels. Furthermore, we show that FGF2, a cytokine commonly used to maintain pluripotency activates pyruvate dehydrogenase through MEK1/2-ERK1/2 signaling pathway-mediated downregulation of ROS in 5% O2, thus promoting histone acetylation. Our results show the importance of pyruvate dehydrogenase in regulating energy metabolism and its connection to pluripotency. Furthermore, our data highlight the role of reactive oxygen species and redox homeostasis in pluripotency maintenance and differentiation.
Highlights- PDP1-induced activation of PDH leads to increased histone H3 pan acetylation and NANOG levels in hPSCs
- Reactive oxygen species (ROS) inactivate PDP1 and decrease histone H3 pan acetylation and NANOG levels in hPSCs
- MEK1/2-ERK1/2 signaling-mediated downregulation of ROS in 5% O2 activates PDH in hPSCs
Graphical abstract
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/524871v1_ufig1.gif" ALT="Figure 1" greater than
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http://biorxiv.org/cgi/content/short/2023.01.20.524871v1?rss=1
Authors: Fojtik, P., Senfluk, M., Holomkova, K., Salykin, A., Gregorova, J., Smak, P., Pes, O., Raska, J., Stetkova, M., Skladal, P., Sedlackova, M., Hampl, A., Bohaciakova, D., Uldrijan, S., Rotrekl, V.
Abstract:
Precise control of pluripotency is a requirement for the safe and effective use of hPSCs in research and therapies. Here we report that pyruvate dehydrogenase upregulates histone H3 pan acetylation and levels of pluripotency marker NANOG in 5% O2. Pyruvate dehydrogenase (PDH) is an essential metabolic switch and a bottleneck for the glycolytic production of acetyl-CoA. Silencing of gene expression showed that PDH is regulated by the activity of its phosphatase PDP1. We show that PDP1 is sensitive to reactive oxygen species-mediated inactivation, leading to the downregulation of H3 pan acetylation and NANOG levels. Furthermore, we show that FGF2, a cytokine commonly used to maintain pluripotency activates pyruvate dehydrogenase through MEK1/2-ERK1/2 signaling pathway-mediated downregulation of ROS in 5% O2, thus promoting histone acetylation. Our results show the importance of pyruvate dehydrogenase in regulating energy metabolism and its connection to pluripotency. Furthermore, our data highlight the role of reactive oxygen species and redox homeostasis in pluripotency maintenance and differentiation.
Highlights- PDP1-induced activation of PDH leads to increased histone H3 pan acetylation and NANOG levels in hPSCs
- Reactive oxygen species (ROS) inactivate PDP1 and decrease histone H3 pan acetylation and NANOG levels in hPSCs
- MEK1/2-ERK1/2 signaling-mediated downregulation of ROS in 5% O2 activates PDH in hPSCs
Graphical abstract
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/524871v1_ufig1.gif" ALT="Figure 1" greater than
View larger version (39K):
org.highwire.dtl.DTLVardef@1d4717forg.highwire.dtl.DTLVardef@678234org.highwire.dtl.DTLVardef@195576borg.highwire.dtl.DTLVardef@19e5684_HPS_FORMAT_FIGEXP M_FIG C_FIG
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Jan 20, 2023
Format:
Podcast episode
Titles in the series (100)
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