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Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation by Ming-Fen Ho; Cheng Zhang; Irene Moon; Joanna Biernacka; Brandon Coombes; Quyen Ngo; Cedric Skillon; Michelle Skime; Tyler Oesterle; Paul E. Croarkin; Victor M. Karpyak; Hu Li; Richard M. Weinshilboum is a Medicine article available to read on EtoBox.

What is Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation about?

## Objective Fibroblast growth factor 21 (FGF21) analogs have been tested as potential therapeutics for substance use disorders. Prior research suggests that FGF21 administration might affect alcohol consumption and reward behaviors. Our recent report showed that plasma FGF21 levels were positively correlated with alcohol use in patients with alcohol use disorder (AUD). FGF21 has a short half-life (0.5–2 h) and crosses the blood–brain barrier. Therefore, we set out to identify molecular mechanisms for both the naïve form of FGF21 and a long-acting FGF21 molecule (PF-05231023) in induced pluripotent stem cell (iPSC)-derived forebrain neurons. ## Methods We performed RNA-seq in iPSC-derived forebrain neurons treated with naïve FGF21 or PF-05231023 at physiologically relevant concentrations. We obtained plasma levels of FGF21 and GABA from our previous AUD clinical trial (n = 442). We performed ELISA for FGF21 in both iPSC-derived forebrain neurons and forebrain organoids. We determined protein interactions using co-immunoprecipitation. Finally, we applied ChIP assays to confirm the occupancy of REST, EZH2 and H3K27me3 by FGF21 using iPSC-derived forebrain neurons with and without dru

Who reads Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation?

Author

Ming-Fen Ho; Cheng Zhang; Irene Moon; Joanna Biernacka; Brandon Coombes; Quyen Ngo; Cedric Skillon; Michelle Skime; Tyler Oesterle; Paul E. Croarkin; Victor M. Karpyak; Hu Li; Richard M. Weinshilboum

Publisher

Elsevier BV

Published

2023

Field

Medicine (Health Sciences)