PLoS ONE (Dec 2010)

An ES-like pluripotent state in FGF-dependent murine iPS cells.

  • Bruno Di Stefano,
  • Christa Buecker,
  • Federica Ungaro,
  • Alessandro Prigione,
  • Hsu-Hsin Chen,
  • Maaike Welling,
  • Maureen Eijpe,
  • Gustavo Mostoslavsky,
  • Paul Tesar,
  • James Adjaye,
  • Niels Geijsen,
  • Vania Broccoli

DOI
https://doi.org/10.1371/journal.pone.0016092
Journal volume & issue
Vol. 5, no. 12
p. e16092

Abstract

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Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.