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

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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
    Don Rix Protein Identification Facility, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, 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
    Present address: Spanish Stem Cell Bank-Andalucian Branch, Instituto de Investigaciones Biomedicas, Granada 18100, Spain.)

  • 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)

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.

Suggested Citation

  • 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, 2007. "IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro," Nature, Nature, vol. 448(7157), pages 1015-1021, August.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7157:d:10.1038_nature06027
    DOI: 10.1038/nature06027
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    Cited by:

    1. Dasol Han & Guojing Liu & Yujeong Oh & Seyoun Oh & Seungbok Yang & Lori Mandjikian & Neha Rani & Maria C. Almeida & Kenneth S. Kosik & Jiwon Jang, 2023. "ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Fei Pei & Li Ma & Junjun Jing & Jifan Feng & Yuan Yuan & Tingwei Guo & Xia Han & Thach-Vu Ho & Jie Lei & Jinzhi He & Mingyi Zhang & Jian-Fu Chen & Yang Chai, 2023. "Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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