IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro Academic Article uri icon

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abstract

  • Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells.

authors

  • Bendall, Sean C
  • Stewart, Morag H
  • Menendez, Pablo
  • George, Dustin
  • Vijayaragavan, Kausalia
  • Werbowetski-Ogilvie, Tamra
  • Ramos-Mejia, Veronica
  • Rouleau, Anne
  • Yang, Jiabi
  • Bossé, Marc
  • Lajoie, Gilles
  • Bhatia, Mick

publication date

  • August 30, 2007