RRC ID 72045
著者 Sim EZ, Enomoto T, Shiraki N, Furuta N, Kashio S, Kambe T, Tsuyama T, Arakawa A, Ozawa H, Yokoyama M, Miura M, Kume S.
タイトル Methionine metabolism regulates pluripotent stem cell pluripotency and differentiation through zinc mobilization.
ジャーナル Cell Rep
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.
巻・号 40(3)
ページ 111120
公開日 2022-7-19
DOI 10.1016/j.celrep.2022.111120
PII S2211-1247(22)00926-3
PMID 35858556
MeSH Cell Differentiation / physiology Methionine / metabolism Pluripotent Stem Cells* / metabolism S-Adenosylmethionine / metabolism Signal Transduction Zinc* / metabolism
IF 8.109
リソース情報
ヒト・動物細胞 201B7(HPS0063)