• Open Access

A Complex Role for FGF-2 in Self-Renewal, Survival, and Adhesion of Human Embryonic Stem Cells

Authors

  • Livia Eiselleova,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    2. Center for Chemical Genetics, Faculty of Medicine, and University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Kamil Matulka,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    2. Center for Chemical Genetics, Faculty of Medicine, and University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Vitezslav Kriz,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Michaela Kunova,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    2. Center for Chemical Genetics, Faculty of Medicine, and University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Zuzana Schmidtova,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Jakub Neradil,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Boris Tichy,

    1. Department of Internal Medicine–Hemato-oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Dana Dvorakova,

    1. Department of Internal Medicine–Hemato-oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Sarka Pospisilova,

    1. Department of Internal Medicine–Hemato-oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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  • Ales Hampl,

    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    2. Center for Chemical Genetics, Faculty of Medicine, and University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    3. Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    4. Center for Cell Therapy and Tissue Repair, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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  • Petr Dvorak

    Corresponding author
    1. Department of Biology, Faculty of Medicine University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    2. Center for Chemical Genetics, Faculty of Medicine, and University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
    3. Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    4. Center for Cell Therapy and Tissue Repair, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
    • Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A6, 62500 Brno, Czech Republic
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    • Telephone: 420-5494-93318, Fax: 420-5494-91327


  • Author contributions: L.E.: collection and assembly of data; K.M.: collection and assembly of data; V.K.: collection and assembly of data; M.K.: collection and assembly of data; Z.S.: collection and assembly of data; J.N.: collection and assembly of data, data analysis; B.T.: collection and assembly of data; D.D.: collection and assembly of data, data analysis; S.P.: data analysis and interpretation; A.H.: financial support, data analysis and interpretation; P.D.: financial support, conception and design, manuscript writing, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS May 14, 2009; available online without subscription through the open access option.

Abstract

The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs. STEM CELLS 2009;27:1847–1857

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