title: Mapping the route from naive pluripotency to lineage specification.
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.
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Tüzer
authors.initials: T
authors.lastname: Kalkan
authors.affiliation: 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.
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D005855:Germ Layers / Q000166:cytology*; D051379:Mice; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C513672:Zfp42 protein, mouse; D014157:Transcription Factors
keywords: embryonic stem cells; epiblast; lineage specification; pluripotency; self-renewal; signalling