title: Formative pluripotency: the executive phase in a developmental continuum.
abstract: 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 naïve 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 naïve 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.
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK austin.smith@cscr.cam.ac.uk.
authors.forename: Austin
authors.identifier: 0000-0002-3029-4682
authors.initials: A
authors.lastname: Smith
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*
keywords: Developmental potential; Embryonic stem cells; Epiblast; Lineage specification; Pluripotency