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Myc depletion induces a pluripotent dormant state mimicking diapause
- Source :
- Cell
- Publication Year :
- 2018
- Publisher :
- Apollo - University of Cambridge Repository, 2018.
-
Abstract
- Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.<br />This work was supported by the FOR2033 and SFB873 funded by the Deutsche Forschungsgemeinschaft (DFG), the Dietmar Hopp Foundation (all to A.T.), and the Wellcome Trust (to A.S.).
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Genes, myc
Biology
General Biochemistry, Genetics and Molecular Biology
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Gene Knockout Techniques
Mice
Transcription (biology)
Protein biosynthesis
Animals
ddc:610
Embryonic Stem Cells
reproductive and urinary physiology
Cell Proliferation
Cell growth
Biochemistry, Genetics and Molecular Biology(all)
Embryo
Embryo, Mammalian
Embryonic stem cell
Molecular biology
Cell biology
Mice, Inbred C57BL
030104 developmental biology
Blastocyst
embryonic structures
Dormancy
Female
Embryonic diapause
Stem cell
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....0541d26265d7db56454e6ccc62fc4cbb
- Full Text :
- https://doi.org/10.17863/cam.20675