期刊
CELL METABOLISM
卷 24, 期 3, 页码 494-501出版社
CELL PRESS
DOI: 10.1016/j.cmet.2016.06.014
关键词
-
资金
- National Research Foundation of Korea
- Korean government (MSIP) [2012R1A3A2048767]
- Education and Research Encouragement Fund of Seoul National University Hospital
- National Research Foundation of Korea [2012R1A3A2048767] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Embryonic stem cells (ESCs) undergo coordinated epigenetic and metabolic changes to differentiate properly. However, the precise mechanisms by which these alterations are fine-tuned in the early stages of differentiation have not been identified. In this study, we demonstrate that phosphoserine aminotransferase 1 (Psat1), an Oct4/Sox2/Nanog (OSN) target protein, regulates changes in alpha-ketoglutarate (alpha-KG), determining the fate of mouse ESCs (mESCs). Maintaining Psat1 levels was essential for mESC self-renewal and pluripotency. Moderate knockdown (KD) of Psat1 in mESCs lowered DNA 50-hydroxymethylcytosine (5'-hmC) and increased histone methylation levels by downregulating permissive amounts of alpha-KG, ultimately accelerating differentiation. We found that intracellular alpha-KG declined transiently during differentiation and that its dysregulation by treatment with dimethyl-alpha-KG impeded differentiation. Further, by in vivo teratoma formation assay, pluripotency of Psat1 KD mESCs was impaired, especially into the ectodermal lineage. Thus, we have established how Psat1 is regulated in maintaining intracellular alpha-KG levels and determining the fate of mESCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据