胚胎干细胞
干细胞
代谢组
细胞生物学
细胞分化
抗坏血酸
氧化磷酸化
代谢组学
生物化学
谷胱甘肽
生物
化学
代谢物
生物信息学
酶
基因
食品科学
作者
Óscar Yanes,Julie Clark,Diana Wong,Gary J. Patti,Antonio Sánchez‐Ruiz,H. Paul Benton,Sunia A. Trauger,Caroline Desponts,Sheng Ding,Gary Siuzdak
摘要
Metabolites offer an important unexplored complementary approach to understanding the pluripotency of stem cells. Using MS-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. On the basis of the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (for example, neuroprotectin D1) and substrates of pro-oxidative reactions (for example, acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells allows them to differentiate in response to in vivo oxidative processes such as inflammation.
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