期刊
SCIENCE
卷 339, 期 6116, 页码 222-226出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1226603
关键词
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资金
- NSS Scholarship from the Agency for Science, Technology and Research, Singapore
- American Cancer Society
- NIH [4R00CA168997-02, RC2HL102815, U01 HL100001, R01 GM56203]
- Damon Runyon Cancer Research Foundation Amgen fellowship
- iPierian Inc.
Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate.
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