title: JAK/STAT3 signalling is sufficient and             dominant over antagonistic cues for the establishment of naive pluripotency.
abstract: Induced pluripotency depends on cooperativity between expression of defined factors                 and the culture environment. The latter also determines the pluripotent cell state,                 that is, naïve or primed. LIF-JAK/STAT3                 signalling was recently shown to be a limiting factor for reprogramming to                 naïve pluripotency. Here we show that sufficient activation of                     JAK/STAT3 overcomes the                 reprogramming block of cell intermediates and enables somatic cell reprogramming in                 absence of otherwise essential pluripotency medium requisites. Activation of FGF-ERK                 signalling, which promotes exit of naïve pluripotent cells from                 self-renewal, does not prevent JAK/STAT3 induced post-implantation epiblast-derived stem cell                 conversion into naïve pluripotency. Moreover, even in the presence of FGF                 plus Activin, which instructs and maintains the primed state, JAK/STAT3 enforces naïve pluripotency in                 epiblast stem cells. We conclude that JAK/STAT3 signalling can be sufficient and dominant over                 antagonistic cues to enable the induction of a naïve pluripotent state.
authors.affiliation: Wellcome Trust Centre for Stem Cell Research, Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Anouk L
authors.initials: AL
authors.lastname: van Oosten
authors.forename: Yael
authors.initials: Y
authors.lastname: Costa
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: José C R
authors.initials: JC
authors.lastname: Silva
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005855:Germ Layers / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050796:STAT3 Transcription Factor; D028341:Activins; D005346:Fibroblast Growth Factors; D053612:Janus Kinases