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Philos Trans R Soc Lond B Biol Sci. 2014 Dec 5;369(1657). pii: 20130540. doi: 10.1098/rstb.2013.0540.

Mapping the route from naive pluripotency to lineage specification.

Author information

1
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
2
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK austin.smith@cscr.cam.ac.uk.

Abstract

In the mouse blastocyst, epiblast cells are newly formed shortly before implantation. They possess a unique developmental plasticity, termed naive pluripotency. For development to proceed, this naive state must be subsumed by multi-lineage differentiation within 72 h following implantation. In vitro differentiation of naive embryonic stem cells (ESCs) cultured in controlled conditions provides a tractable system to dissect and understand the process of exit from naive pluripotency and entry into lineage specification. Exploitation of this system in recent large-scale RNAi and mutagenesis screens has uncovered multiple new factors and modules that drive or facilitate progression out of the naive state. Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. Here, we summarize these findings and propose a road map for state transitions in ESC differentiation that reflects the orderly dynamics of epiblast progression in the embryo.

KEYWORDS:

embryonic stem cells; epiblast; lineage specification; pluripotency; self-renewal; signalling

PMID:
25349449
PMCID:
PMC4216463
DOI:
10.1098/rstb.2013.0540
[Indexed for MEDLINE]
Free PMC Article

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