Integrin-associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment and Differentiation

Loriana Vitillo, Melissa Baxter, Banu Iskender, Paul Whiting, Susan Kimber

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Human embryonic stem cells (hESCs) can be maintained in a fully defined niche on extracellular matrix substrates, to which they attach through integrin receptors. However, the underlying integrin signaling mechanisms, and their contribution to hESC behavior, are largely unknown. Here, we show that focal adhesion kinase (FAK) transduces integrin activation and supports hESC survival, substrate adhesion, and maintenance of the undifferentiated state. After inhibiting FAK kinase activity we show that hESCs undergo cell detachment-dependent apoptosis or differentiation. We also report deactivation of FAK downstream targets, AKT and MDM2, and upregulation of p53, all key players in hESC regulatory networks. Loss of integrin activity or FAK also induces cell aggregation, revealing a role in the cell-cell interactions of hESCs. This study provides insight into the integrin signaling cascade activated in hESCs and reveals in FAK a key player in the maintenance of hESC survival and undifferentiated state.
    Original languageEnglish
    JournalStem Cell Reports
    Volume7
    Issue number2
    Early online date9 Aug 2016
    DOIs
    Publication statusPublished - 9 Aug 2016

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