Open AccessTracking the embryonic stem cell transition from ground state pluripotency
Author(s) -
Tüzer Kalkan,
Nelly Olova,
Mila Roode,
Carla Mulas,
Heather Lee,
Isabelle Nett,
Hendrik Marks,
Rachael Walker,
Hendrik G. Stunnenberg,
Kathryn S. Lilley,
Jennifer Nichols,
Wolf Reik,
Paul Bertone,
Austin Smith
Publication year - 2017
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.142711
Subject(s) - epiblast , biology , embryonic stem cell , microbiology and biotechnology , stem cell , population , genetics , gastrulation , gene , demography , sociology
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.