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

Nat Commun. 2012 May 8:3:817. doi: 10.1038/ncomms1822.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / antagonists & inhibitors
  • Activins / metabolism
  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Female
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / metabolism
  • Germ Layers / cytology
  • Germ Layers / enzymology
  • Germ Layers / metabolism
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / enzymology
  • Induced Pluripotent Stem Cells / metabolism*
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*

Substances

  • STAT3 Transcription Factor
  • Activins
  • Fibroblast Growth Factors
  • Janus Kinases

Associated data

  • GEO/GSE36818