JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency

Anouk L. van Oosten, Yael Costa, Austin Smith and José C.R. Silva ()
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Anouk L. van Oosten: Wellcome Trust Centre for Stem Cell Research, Stem Cell Institute, University of Cambridge
Yael Costa: Wellcome Trust Centre for Stem Cell Research, Stem Cell Institute, University of Cambridge
Austin Smith: Wellcome Trust Centre for Stem Cell Research, Stem Cell Institute, University of Cambridge
José C.R. Silva: Wellcome Trust Centre for Stem Cell Research, Stem Cell Institute, University of Cambridge

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms1822

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