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@ARTICLE{Scognamiglio:130534,
author = {R. Scognamiglio$^*$ and N. Cabezas-Wallscheid$^*$ and M.
Thier$^*$ and S. Altamura and A. Reyes and A.
Prendergast$^*$ and D. Baumgärtner$^*$ and L. S.
Carnevalli$^*$ and A. Atzberger and S. Haas$^*$ and L. von
Paleske$^*$ and T. Boroviak and P. Wörsdörfer and M.
Essers$^*$ and U. Kloz$^*$ and R. N. Eisenman and F.
Edenhofer and P. Bertone and W. Huber and F. van der
Hoeven$^*$ and A. Smith and A. Trumpp$^*$},
title = {{M}yc {D}epletion {I}nduces a {P}luripotent {D}ormant
{S}tate {M}imicking {D}iapause.},
journal = {Cell},
volume = {164},
number = {4},
issn = {0092-8674},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DKFZ-2017-05613},
pages = {668 - 680},
year = {2016},
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 = {Myc protein, mouse (NLM Chemicals) / Proto-Oncogene
Proteins c-myc (NLM Chemicals)},
cin = {V960 / A010 / A011 / W450 / L101},
ddc = {570},
cid = {I:(DE-He78)V960-20160331 / I:(DE-He78)A010-20160331 /
I:(DE-He78)A011-20160331 / I:(DE-He78)W450-20160331 /
I:(DE-He78)L101-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26871632},
pmc = {pmc:PMC4752822},
doi = {10.1016/j.cell.2015.12.033},
url = {https://inrepo02.dkfz.de/record/130534},
}