Early gene regulation of osteogenesis in embryonic stem cells

Glen R. Kirkham, Anna Lovrics, Helen M. Byrne, Oliver E. Jensen, John R. King, Kevin M. Shakesheff, Lee D K Buttery

    Research output: Contribution to journalArticlepeer-review


    The early gene regulatory networks (GRNs) that mediate stem cell differentiation are complex, and the underlying regulatory associations can be difficult to map accurately. In this study, the expression profiles of the genes Dlx5, Msx2 and Runx2 in mouse embryonic stem cells were monitored over a 48 hour period after exposure to the growth factors BMP2 and TGFβ1. Candidate GRNs of early osteogenesis were constructed based on published experimental findings and simulation results of Boolean and ordinary differential equation models were compared with our experimental data in order to test the validity of these models. Three gene regulatory networks were found to be consistent with the data, one of these networks exhibited sustained oscillation, a behaviour which is consistent with the general view of embryonic stem cell plasticity. The work cycle presented in this paper illustrates how mathematical modelling can be used to elucidate from gene expression profiles GRNs that are consistent with experimental data. © 2012 The Royal Society of Chemistry.
    Original languageEnglish
    Pages (from-to)1470-1477
    Number of pages7
    JournalIntegrative Biology (United Kingdom)
    Issue number12
    Publication statusPublished - Dec 2012


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