RRC ID |
72045
|
Author |
Sim EZ, Enomoto T, Shiraki N, Furuta N, Kashio S, Kambe T, Tsuyama T, Arakawa A, Ozawa H, Yokoyama M, Miura M, Kume S.
|
Title |
Methionine metabolism regulates pluripotent stem cell pluripotency and differentiation through zinc mobilization.
|
Journal |
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.
|
Volume |
40(3)
|
Pages |
111120
|
Published |
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
|
Resource |
Human and Animal Cells |
201B7(HPS0063) |