Year: 2017
Type: article
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.
Source: Development
DOI: 10.1242/dev.142711
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,781
Awards: To study epigenetic mechanisms that create heterogeneity and functional diversity in stem cells, development and between individuals, G2227879678, Wellcome Trust MRC Cambridge Stem Cell Institute, The Road from Pluripotency to Lineage Determination., G3725617714, Adaptation of a high resolution, high throughput assay of immunoglobulin repertoires for commercial and clinical applications, FP7 Network of Excellence EpiGeneSys: Epigenetics towards systems biology, European Consortium for Systematic Stem Cell Biology, G6895601894, Epigenetic reprogramming in mammalian development., G7378106769, G7798231803, Stem Cell Derivation, Differentiation and Transplantation, G8500365153, G8525317206, Comparative transcriptional control of establishment, maintenance and collapse of naive pluripotency in rodents and primates in vivo
OpenAlex ID: W2951213089