Wu Haibo, Song Chao, Zhang Jingcheng, Zhao Jiamin, Fu Beibei, Mao Tingchao, Zhang Yong
College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
FASEB J. 2017 Apr;31(4):1731-1743. doi: 10.1096/fj.201601085R. Epub 2017 Jan 9.
Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stem cells (iPSCs). However, the effects of the combined treatment of vitamin C and melatonin on the differentiation of embryonic stem cells (ESCs) have not yet been examined. In this study, we showed that melatonin synergizes with vitamin C to derail exit from pluripotency of mouse ESCs. This effect is related to the increased uptake of dehydroascorbate, the oxidized form of vitamin C, through glucose transporter 1 (Glut1) transporter, which in turn, is upregulated by melatonin treatment. Analysis of the cell signaling pathway profiling systems and specific pathway inhibition indicated that melatonin enhances Glut1 expression by activating the PI3K/AKT and MAPK/ERK signaling pathways. Our findings provide a theoretical basis for application of melatonin in research on ESCs and iPSCs and for further investigation of the effect of combinatorial compounds on cell reprogramming.-Wu, H., Song, C., Zhang, J., Zhao, J., Fu, B., Mao, T., Zhang, Y. Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells.
褪黑素和维生素C是强大的抗氧化剂，可提高诱导多能干细胞（iPSC）的重编程效率。然而，维生素C和褪黑素联合处理对胚胎干细胞（ESC）分化的影响尚未得到研究。在本研究中，我们发现褪黑素与维生素C协同作用，使小鼠ESC偏离多能性退出。这种效应与通过葡萄糖转运蛋白1（Glut1）转运体增加维生素C的氧化形式脱氢抗坏血酸的摄取有关，而Glut1转运体又通过褪黑素处理上调。对细胞信号通路分析系统和特定通路抑制的分析表明，褪黑素通过激活PI3K/AKT和MAPK/ERK信号通路增强Glut1表达。我们的研究结果为褪黑素在ESC和iPSC研究中的应用以及进一步研究组合化合物对细胞重编程的影响提供了理论基础。-吴，H.，宋，C.，张，J.，赵，J.，傅，B.，毛，T.，张，Y.褪黑素介导的GLUT1上调通过增加小鼠胚胎干细胞中氧化型维生素C的摄取来阻止多能性退出。
