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

Authors :
Chunaram Choudhary
Benjamin A. Garcia
Thomas L. Saunders
Le Tran Phuc Khoa
Natarajan V. Bhanu
Fengbiao Mao
Li Zhang
Xin Tong
Yao-Chang Tsan
Stephanie L. Bielas
Daniel M. Kremer
Peter Sajjakulnukit
Lei Yin
Gary D. Smith
Costas A. Lyssiotis
Bo Zhou
Yali Dou
Source :
Cell Stem Cell
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Summary 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.

Details

ISSN :
19345909
Volume :
27
Database :
OpenAIRE
Journal :
Cell Stem Cell
Accession number :
edsair.doi.dedup.....7f1ab73fc36c7b25f5f7f512b54b3590
Full Text :
https://doi.org/10.1016/j.stem.2020.06.005