title: Nanog is the gateway to the pluripotent ground state.
abstract: Pluripotency is generated naturally during mammalian development through formation of the epiblast, founder tissue of the embryo proper. Pluripotency can be recreated by somatic cell reprogramming. Here we present evidence that the homeodomain protein Nanog mediates acquisition of both embryonic and induced pluripotency. Production of pluripotent hybrids by cell fusion is promoted by and dependent on Nanog. In transcription factor-induced molecular reprogramming, Nanog is initially dispensable but becomes essential for dedifferentiated intermediates to transit to ground state pluripotency. In the embryo, Nanog specifically demarcates the nascent epiblast, coincident with the domain of X chromosome reprogramming. Without Nanog, pluripotency does not develop, and the inner cell mass is trapped in a pre-pluripotent, indeterminate state that is ultimately nonviable. These findings suggest that Nanog choreographs synthesis of the naive epiblast ground state in the embryo and that this function is recapitulated in the culmination of somatic cell reprogramming.
authors.affiliation: Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK. jcs64@cscr.cam.ac.uk
authors.forename: Jose
authors.initials: J
authors.lastname: Silva
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nichols
authors.forename: Thorold W
authors.initials: TW
authors.lastname: Theunissen
authors.forename: Ge
authors.initials: G
authors.lastname: Guo
authors.forename: Anouk L
authors.initials: AL
authors.lastname: van Oosten
authors.forename: Ornella
authors.initials: O
authors.lastname: Barrandon
authors.forename: Jason
authors.initials: J
authors.lastname: Wray
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Ian
authors.initials: I
authors.lastname: Chambers
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D001755:Blastocyst / Q000166:cytology; D054337:Cell Dedifferentiation; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005855:Germ Layers / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000071317:Nanog Homeobox Protein; D014960:X Chromosome / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse
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