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

Sean C. Bendall, Morag H. Stewart, Pablo Menendez, Dustin George, Kausalia Vijayaragavan, Tamra Werbowetski-Ogilvie, Veronica Ramos-Mejia, Anne Rouleau, Jiabi Yang, Marc Bossé, Gilles Lajoie and Mickie Bhatia ()
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Sean C. Bendall: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Morag H. Stewart: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Pablo Menendez: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Dustin George: Don Rix Protein Identification Facility, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
Kausalia Vijayaragavan: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Tamra Werbowetski-Ogilvie: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Veronica Ramos-Mejia: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Anne Rouleau: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Jiabi Yang: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Marc Bossé: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Gilles Lajoie: Don Rix Protein Identification Facility, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
Mickie Bhatia: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada

Nature, 2007, vol. 448, issue 7157, 1015-1021

Abstract: 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.

Date: 2007
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DOI: 10.1038/nature06027

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