TY  - JOUR
AU  - Scognamiglio, Roberta
AU  - Cabezas-Wallscheid, Nina
AU  - Thier, Marc
AU  - Altamura, Sandro
AU  - Reyes, Alejandro
AU  - Prendergast, Aine
AU  - Baumgärtner, Daniel
AU  - Carnevalli, Larissa S
AU  - Atzberger, Ann
AU  - Haas, Simon
AU  - von Paleske, Lisa
AU  - Boroviak, Thorsten
AU  - Wörsdörfer, Philipp
AU  - Essers, Marieke
AU  - Kloz, Ulrich
AU  - Eisenman, Robert N
AU  - Edenhofer, Frank
AU  - Bertone, Paul
AU  - Huber, Wolfgang
AU  - van der Hoeven, Franciscus
AU  - Smith, Austin
AU  - Trumpp, Andreas
TI  - Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause.
JO  - Cell
VL  - 164
IS  - 4
SN  - 0092-8674
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DKFZ-2017-05613
SP  - 668 - 680
PY  - 2016
AB  - 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.
KW  - Myc protein, mouse (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-myc (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26871632
C2  - pmc:PMC4752822
DO  - DOI:10.1016/j.cell.2015.12.033
UR  - https://inrepo02.dkfz.de/record/130534
ER  -