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

PLoS One. 2010 Dec 30;5(12):e16092. doi: 10.1371/journal.pone.0016092.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Embryo Culture Techniques*
  • Embryonic Stem Cells / cytology*
  • Fibroblast Growth Factors / metabolism*
  • Fibroblasts / metabolism
  • Green Fluorescent Proteins / metabolism
  • Induced Pluripotent Stem Cells / cytology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Retroviridae / genetics
  • Species Specificity
  • Teratoma / genetics
  • X Chromosome

Substances

  • Intercellular Signaling Peptides and Proteins
  • Green Fluorescent Proteins
  • Fibroblast Growth Factors