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Methionine metabolism regulates pluripotent stem cell pluripotency and differentiation through zinc mobilization

Sim, Erinn Zixuan Enomoto, Takayuki Shiraki, Nobuaki Furuta, Nao Kashio, Soshiro Kambe, Taiho Tsuyama, Tomonori Arakawa, Akihiro Ozawa, Hiroki Yokoyama, Mizuho Miura, Masayuki Kume, Shoen 京都大学 DOI:10.1016/j.celrep.2022.111120

2022.07

概要

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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参考文献

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