Journal
CELL REPORTS
Volume 40, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.111120
Keywords
methionine metabolism; Methionine; intracellular protein -bound Zn; Zn
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Funding
- Project for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan [21H02978, 18H02154, 21H04774]
- Danone Institute research project
- Takeda Science Foundation
- Japanese Insulin Dependent Diabetes Mellitus (IDDM) Network Foundation
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The study found that methionine deprivation triggers a reduction in intracellular Zn content and upregulation of Zn exporter, leading to differentiation. PSCs cultured under Zn deprivation exhibit slowed cell growth and altered methionine metabolism-related metabolite profile.
Pluripotent stem cells (PSCs) exhibit a unique feature that requires S-adenosylmethionine (SAM) for the main-tenance 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 b 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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