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Updated: Sep 4, 2025

An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
Methionine metabolism regulates pluripotent stem cell pluripotency and differentiation through zinc mobilization
Erinn Zixuan Sim1, Takayuki Enomoto1, Nobuaki Shiraki1
1School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
Abstract:
Pluripotent stem cells (PSCs) exhibit a unique feature that requires S-adenosylmethionine (SAM) for the maintenance of their pluripotency. Methionine deprivation in the medium causes a reduction in intracellular SAM, thus rendering PSCs in a state potentiated for differentiation. In this study, we find that methionine deprivation triggers a reduction in intracellular protein-bound Zn content and upregulation of Zn exporter SLC30A1 in PSCs. Culturing PSCs in Zn-deprived medium results in decreased intracellular protein-bound Zn content, reduced cell growth, and potentiated differentiation, which partially mimics methionine deprivation. PSCs cultured under Zn deprivation exhibit an altered methionine metabolism-related metabolite profile. We conclude that methionine deprivation potentiates differentiation partly by lowering cellular Zn content. We establish a protocol to generate functional pancreatic β cells by applying methionine and Zn deprivation. Our results reveal a link between Zn signaling and methionine metabolism in the regulation of cell fate in PSCs.
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