title: Early gene regulation of osteogenesis in embryonic stem cells.
abstract: 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.
authors.affiliation: Centre for Biomolecular Sciences, University Park, Nottingham, UK. glen.kirkham@nottingham.ac.uk
authors.forename: Glen R
authors.initials: GR
authors.lastname: Kirkham
authors.forename: Anna
authors.initials: A
authors.lastname: Lovrics
authors.forename: Helen M
authors.initials: HM
authors.lastname: Byrne
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Jensen
authors.forename: John R
authors.initials: JR
authors.lastname: King
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
authors.forename: Lee D K
authors.initials: LD
authors.lastname: Buttery
mesh_terms: D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; C084119:MSX2 protein; C493716:Runx2 protein, mouse; D053773:Transforming Growth Factor beta1; D012313:RNA