Journal
DEVELOPMENT
Volume 144, Issue 3, Pages 365-373Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.142679
Keywords
Embryonic stem cells; Pluripotency; Epiblast; Lineage specification; Developmental potential
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Funding
- Medical Research Council
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- European Commission Project PluriMes
- Medical Research Council [MC_PC_12009, G1100526] Funding Source: researchfish
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The regulative capability of single cells to give rise to all primary embryonic lineages is termed pluripotency. Observations of fluctuating gene expression and phenotypic heterogeneity in vitro have fostered a conception of pluripotency as an intrinsically metastable and precarious state. However, in the embryo and in defined culture environments the properties of pluripotent cells change in an orderly sequence. Two phases of pluripotency, called naive and primed, have previously been described. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the naive and primed phases. The formative phase is hypothesised to be enabling for the execution of pluripotency, entailing remodelling of transcriptional, epigenetic, signalling and metabolic networks to constitute multi-lineage competence and responsiveness to specification cues.
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