Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells

作者：Wu, Haibo^*; Song, Chao; Zhang, Jingcheng; Zhao, Jiamin; Fu, Beibei; Mao, Tingchao; Zhang, Yong^*

来源：The FASEB Journal, 2017, 31(4): 1731-1743.

DOI：10.1096/fj.201601085R

• dehydroascorbic acid
• glucose transporter 1
• signaling pathway
• differentiation

Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stemcells (iPSCs). However, the effects of the combined treatment of vitamin C andmelatonin 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 andspecificpathwayinhibitionindicatedthatmelatoninenhancesGlut1 expressionby activating thePI3K/AKT andMAPK/ERK signaling pathways. Our findings provide a theoretical basis for application ofmelatonin 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 frompluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells. FASEB J. 31, 1731-1743 (2017). www.fasebj.org

• 出版日期2017-4
• 单位西北农林科技大学