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Histone Acetyltransferase MOF Blocks Acquisition of Quiescence in Ground-State ESCs through Activating Fatty Acid Oxidation.

Abstract：

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

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Khoa LTP,Tsan YC,Mao F,Kremer DM,Sajjakulnukit P,Zhang L,Zhou B,Tong X,Bhanu NV,Choudhary C,Garcia BA,Yin L,Smith GD,Saunders TL,Bielas SL,Lyssiotis CA,Dou Y

doi

10.1016/j.stem.2020.06.005

subject

Has Abstract

pub_date

2020-09-03 00:00:00

pages

441-458.e10

issue

3

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(20)30272-1

journal_volume

27

pub_type

杂志文章

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