| 論文作者 |
Shao, M; Wang, H; Liu, YJ; Wang, YQ; Zhao, HZ; Gu, JJ; Zhong, N; Zhou, YF; Yin, HY; Jin, Y; Liao, B |
| 摘要 |
Na & iuml;ve human embryonic stem cells (hESCs) possess some advantages over their primed counterparts, displaying distinctive metabolic and epigenetic properties. However, the master regulator governing these features remains unrecognized. Here, we systematically investigate functions of the core transcription factor NANOG in na & iuml;ve hESCs. Acting as an upstream key regulator, NANOG directly activates genes associated with na & iuml;ve pluripotency, acetyl-CoA synthesis and anti-oxidation in a na & iuml;ve pluripotency state- dependent manner, and represses the expression of extraembryonic lineage genes in na & iuml;ve hESCs. NANOG modulates transcription of multiple genes in various pathways of acetyl-CoA synthesis, maintains the intracellular acetyl-CoA level and characteristic epigenetic landscapes, particularly the high level of histone acetylation, in na & iuml;ve hESCs. NANOG is indispensable for the high activity of both OXPHOS and glycolysis, a bivalent metabolic state typical in na & iuml;ve hESCs. Furthermore, we identify GPX2 as a mediator of NANOG in sustaining redox balance and survival of na & iuml;ve hESCs. Together, this study reveals previously unrecognized roles of NANOG in orchestrating transcriptional, metabolic and epigenetic signatures to secure human na & iuml;ve pluripotency. |
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