Tracking the embryonic stem cell transition from ground state pluripotency

Tüzer Kalkan*, Nelly Olova, Mila Roode, Carla Mulas, Heather J. Lee, Isabelle Nett, Hendrik Marks, Rachael Walker, Hendrik G. Stunnenberg, Kathryn S. Lilley, Jennifer Nichols, Wolf Reik, Paul Bertone, Austin Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)1221-1234
Number of pages14
JournalDevelopment (Cambridge)
Volume144
Issue number7
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • Epiblast
  • ES cells
  • Methylome
  • Pluripotency
  • Rex1
  • Transcriptome

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