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.
Original language | English |
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Pages (from-to) | 1221-1234 |
Number of pages | 14 |
Journal | Development (Cambridge) |
Volume | 144 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Apr 2017 |
Keywords
- Epiblast
- ES cells
- Methylome
- Pluripotency
- Rex1
- Transcriptome