美国加州大学洛杉矶分校Yali Dou研究团队发现，组蛋白乙酰转移酶MOF通过激活脂肪酸氧化来阻止基态ESC静止的发生。2020年6月30日，《细胞—干细胞》杂志在线发表了这项成果。

Author: Le Tran Phuc Khoa, Yao-Chang Tsan, Fengbiao Mao, Daniel M. Kremer, Peter Sajjakulnukit, Li Zhang, Bo Zhou, Xin Tong, Natarajan V. Bhanu, Chunaram Choudhary, Benjamin A. Garcia, Lei Yin, Gary D. Smith, Thomas L. Saunders, Stephanie L. Bielas, Costas A. Lyssiotis, Yali Dou

Issue&Volume: 2020-06-30

Abstract: Self-renewing embryonic stem cells (ESCs) respond to environmental cues by exitingpluripotency or entering a quiescent state. The molecular basis underlying this fatechoice remains unclear. Here, we show that histone acetyltransferase MOF plays a criticalrole in this process through directly activating fatty acid oxidation (FAO) in theground-state ESCs. We further show that the ground-state ESCs particularly rely onelevated FAO for oxidative phosphorylation (OXPHOS) and energy production. Mof deletion or FAO inhibition induces bona fide quiescent ground-state ESCs with anintact core pluripotency network and transcriptome signatures akin to the diapausedepiblasts in vivo. Mechanistically, MOF/FAO inhibition acts through reducing mitochondrial respiration(i.e., OXPHOS), which in turn triggers reversible pluripotent quiescence specificallyin the ground-state ESCs. The inhibition of FAO/OXPHOS also induces quiescence innaive human ESCs. Our study suggests a general function of the MOF/FAO/OXPHOS axisin regulating cell fate determination in stem cells.

DOI: 10.1016/j.stem.2020.06.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30272-1