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000130534 0247_ $$2doi$$a10.1016/j.cell.2015.12.033
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000130534 1001_ $$0P:(DE-He78)e71131deb6a162322ed90cb14da7a50e$$aScognamiglio, Roberta$$b0$$eFirst author$$udkfz
000130534 245__ $$aMyc Depletion Induces a Pluripotent Dormant State Mimicking Diapause.
000130534 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2016
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000130534 520__ $$aMouse 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.
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000130534 650_7 $$2NLM Chemicals$$aMyc protein, mouse
000130534 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-myc
000130534 7001_ $$0P:(DE-HGF)0$$aCabezas-Wallscheid, Nina$$b1
000130534 7001_ $$0P:(DE-He78)6257f38db66cdb3a0d6fdab856728545$$aThier, Marc$$b2$$udkfz
000130534 7001_ $$aAltamura, Sandro$$b3
000130534 7001_ $$aReyes, Alejandro$$b4
000130534 7001_ $$0P:(DE-He78)a071b452400f4a34fc58fa5db64b3012$$aPrendergast, Aine$$b5$$udkfz
000130534 7001_ $$0P:(DE-HGF)0$$aBaumgärtner, Daniel$$b6
000130534 7001_ $$0P:(DE-HGF)0$$aCarnevalli, Larissa S$$b7
000130534 7001_ $$0P:(DE-HGF)0$$aAtzberger, Ann$$b8
000130534 7001_ $$0P:(DE-He78)a5ec4e2fef99022a37a6b07c2fdd6325$$aHaas, Simon$$b9$$udkfz
000130534 7001_ $$0P:(DE-He78)ad009253d266295ec14c8cb708d87163$$avon Paleske, Lisa$$b10$$udkfz
000130534 7001_ $$aBoroviak, Thorsten$$b11
000130534 7001_ $$aWörsdörfer, Philipp$$b12
000130534 7001_ $$0P:(DE-He78)ba3fae49054b6bfaaa289b05ecd936d6$$aEssers, Marieke$$b13$$udkfz
000130534 7001_ $$0P:(DE-He78)1a5f84c92367a0ab8dffdd2d3619e234$$aKloz, Ulrich$$b14$$udkfz
000130534 7001_ $$aEisenman, Robert N$$b15
000130534 7001_ $$aEdenhofer, Frank$$b16
000130534 7001_ $$aBertone, Paul$$b17
000130534 7001_ $$aHuber, Wolfgang$$b18
000130534 7001_ $$0P:(DE-He78)db41d10e17712fc21628c50a14f4d507$$avan der Hoeven, Franciscus$$b19$$udkfz
000130534 7001_ $$aSmith, Austin$$b20
000130534 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b21$$eLast author$$udkfz
000130534 773__ $$0PERI:(DE-600)2001951-8$$a10.1016/j.cell.2015.12.033$$gVol. 164, no. 4, p. 668 - 680$$n4$$p668 - 680$$tCell$$v164$$x0092-8674$$y2016
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