p53 coordinates glucose and choline metabolism during the mesendoderm differentiation of human embryonic stem cells
p53 coordinates glucose and choline metabolism during the mesendoderm differentiation of human embryonic stem cells
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p53 在人胚胎干细胞中内胚层分化过程中协调葡萄糖和胆碱代谢。
DOI：
10.1016/j.scr.2020.102067
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发表时间：
2020
影响因子：
1.2
通讯作者：
Yang Xu
中科院分区：
文献类型：
--
作者：
Gaoyang Zhu;Yue Ying;Kaiyuan Ji;Xinyue Duan;Taoyi Mai;Jinchul Kim;Qingjiao Li;Lili Yu;Yang Xu
新陈代谢在决定人胚胎干细胞(HESCs)命运中起着至关重要的作用。在这里，我们发现hESCs中P53的缺失增强了糖酵解，减少了氧化磷酸化，并延缓了hESCs的中胚层分化。更有趣的是，hESCs中p53的破坏导致hESCs多潜能状态和分化状态下磷脂酰胆碱的显著上调和总胆碱的减少，这表明在没有p53的情况下胆碱代谢异常。总而言之，我们的研究揭示了p53在协调糖和脂代谢以维持适当的hESC身份方面不可或缺的作用。
Metabolism plays crucial roles in the fate decision of human embryonic stem cells (hESCs). Here, we show that the depletion of p53 in hESCs enhances glycolysis and reduces oxidative phosphorylation, and delays mesendoderm differentiation of hESCs. More intriguingly, the disruption of p53 in hESCs leads to dramatic upregulation of phosphatidylcholine and decrease of total choline in both pluripotent and differentiated state of hESCs, suggesting abnormal choline metabolism in the absence of p53. Collectively, our study reveals the indispensable role of p53 in orchestrating both glucose and lipid metabolism to maintain proper hESC identity.