Metabolic oxidation regulates embryonic stem cell differentiation.
Metabolic oxidation regulates embryonic stem cell differentiation.
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DOI：
10.1038/nchembio.364
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发表时间：
2010-06
影响因子：
14.8
通讯作者：
Siuzdak G
中科院分区：
文献类型：
--
作者：
Yanes O;Clark J;Wong DM;Patti GJ;Sánchez-Ruiz A;Benton HP;Trauger SA;Desponts C;Ding S;Siuzdak G
Metalloprotein为理解干细胞的多能性提供了一个重要的未探索的补充。使用基于质谱的代谢组学，我们表明胚胎干细胞的特征是含有丰富的具有高度不饱和结构的代谢物，其水平在分化时降低。通过监测还原型和氧化型谷胱甘肽的比例以及抗坏血酸水平，我们证明了干细胞的氧化还原状态在分化过程中受到调节。基于不饱和代谢物的氧化生物化学，我们在实验上操纵胚胎干细胞中的特定途径，同时监测对分化的影响。类花生酸信号通路的抑制促进了多能性并维持了不饱和脂肪酸的水平。相反，下游氧化代谢物（例如，神经保护素D1）和促氧化反应的底物（例如，酰基-肉毒碱），促进神经元和心脏分化。我们推测，干细胞维持的高度不饱和代谢组使它们特别适应于体内氧化过程（如炎症）的分化。
Metabolites offer an important unexplored complement to understanding the pluripotency of stem cells. Using mass spectrometry-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. Based on 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 (e.g., neuroprotectin D1) and substrates of pro-oxidative reactions (e.g., acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells makes them particularly attuned to differentiate in response to in vivo oxidative processes such as inflammation.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
2.7
作者：
CORDEAULOSSOUARN, L;VAYSSIERE, JL;CROIZAT, B
通讯作者：
CROIZAT, B
DOI：
10.1096/fj.06-7227rev
发表时间：
2007-02
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Serhan CN;Brain SD;Buckley CD;Gilroy DW;Haslett C;O'Neill LA;Perretti M;Rossi AG;Wallace JL
通讯作者：
Wallace JL
影响因子：
5
作者：
IDELLWENGER, JA;GROTYOHANN, LW;NEELY, JR
通讯作者：
NEELY, JR
DOI：
10.1073/pnas.89.23.11566
发表时间：
1992-12-01
影响因子：
11.1
作者：
MARTENSSON, J;MEISTER, A
通讯作者：
MEISTER, A