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Development. 2017 Apr 1;144(7):1221-1234. doi: 10.1242/dev.142711. Epub 2017 Feb 7.

Tracking the embryonic stem cell transition from ground state pluripotency.

Author information

1
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK tk360@cam.ac.uk austin.smith@cscr.cam.ac.uk.
2
Babraham Institute, Cambridge CB22 3AT, UK.
3
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK.
4
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
5
Radboud University, Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen 6500HB, The Netherlands.
6
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
7
The Cambridge Centre for Proteomics, Cambridge System Biology Centre, University of Cambridge, Cambridge CB2 1QR, UK.
8
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 4BG, UK.
9
Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.

Abstract

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 naïve pluripotency. Here, we examine 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 naïve 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 naïve cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.

KEYWORDS:

ES cells; Epiblast; Methylome; Pluripotency; Rex1; Transcriptome

PMID:
28174249
PMCID:
PMC5399622
DOI:
10.1242/dev.142711
[Indexed for MEDLINE]
Free PMC Article

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