Repository logo

Tracking the embryonic stem cell transition from ground state pluripotency

Published version

Change log


Kalkan, T 
Olova, N 
Roode, M 
Lee, HJ 


Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here we examined the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naive cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.



ES cells, Rex1, methylome, epiblast, pluripotency, transcriptome

Journal Title


Conference Name

Journal ISSN


Volume Title



The Company of Biologists
Medical Research Council (MC_PC_12009)
MRC (G1100526)
Wellcome Trust (091484/Z/10/Z)
Biotechnology and Biological Sciences Research Council (BB/M004023/1)
This research was funded by the Wellcome Trust (091484/Z/10/Z and 095645/Z/11/Z), the Biotechnology and Biological Sciences Research Council (BB/M004023/1 and BB/K010867/1), a European Commission Framework 7 project EuroSyStem (HEALTH-F4-2007-200720 EUROSYSTEM), SysStemCell (ERC-2013-AdG 339431), the Medical Research Council (MRC) (G1100526/1) the Louis-Jeantet Foundation and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO-VIDI 864.12.007). The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and Medical Research Council (MRC). A.S. is an MRC Professor. Deposited in PMC for immediate release.