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Histone Acetyltransferase MOF Blocks Acquisition of Quiescence in Ground-State ESCs through Activating Fatty Acid Oxidation
- 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.
- Subjects :
- Oxidative phosphorylation
Cell fate determination
Article
Transcriptome
03 medical and health sciences
0302 clinical medicine
Genetics
Humans
Epigenetics
Beta oxidation
Embryonic Stem Cells
reproductive and urinary physiology
Histone Acetyltransferases
030304 developmental biology
0303 health sciences
biology
Fatty Acids
digestive, oral, and skin physiology
food and beverages
Cell Differentiation
Cell Biology
Histone acetyltransferase
Embryonic stem cell
Cell biology
embryonic structures
biology.protein
Molecular Medicine
Stem cell
Cell Division
030217 neurology & neurosurgery
Subjects
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