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Myc depletion induces a pluripotent dormant state mimicking diapause

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Item Type:Article
Title:Myc depletion induces a pluripotent dormant state mimicking diapause
Creators Name:Scognamiglio, R. and Cabezas-Wallscheid, N. and Thier, M.C. and Altamura, S. and Reyes, A. and Prendergast, Á.M. and Baumgärtner, D. and Carnevalli, L.S. and Atzberger, Ann and Haas, S. and von Paleske, L. and Boroviak, T. and Wörsdörfer, P. and Essers, M.A.G. and Kloz, U. and Eisenman, R.N. and Edenhofer, F. and Bertone, P. and Huber, W. and van der Hoeven, F. and Smith, A. and Trumpp, A.
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.
Keywords:Blastocyst, Cell Proliferation, Embryonic Stem Cells, Gene Knockout Techniques, Inbred C57BL Mice, Mammalian Embryo, myc Genes, Proto-Oncogene Proteins c-myc, Animals, Mice
Publisher:Cell Press
Page Range:668-680
Date:11 February 2016
Official Publication:https://doi.org/10.1016/j.cell.2015.12.033
PubMed:View item in PubMed

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