Early gene regulation of osteogenesis in embryonic stem cells

Handle URI:
http://hdl.handle.net/10754/598045
Title:
Early gene regulation of osteogenesis in embryonic stem cells
Authors:
Kirkham, Glen R.; Lovrics, Anna; Byrne, Helen M.; Jensen, Oliver E.; King, John R.; Shakesheff, Kevin M.; Buttery, Lee D. K.
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. © 2012 The Royal Society of Chemistry.
Citation:
Kirkham GR, Lovrics A, Byrne HM, Jensen OE, King JR, et al. (2012) Early gene regulation of osteogenesis in embryonic stem cells. Integrative Biology 4: 1470. Available: http://dx.doi.org/10.1039/c2ib20164j.
Publisher:
Royal Society of Chemistry (RSC)
Journal:
Integrative Biology
KAUST Grant Number:
KUK-C1-013-03
Issue Date:
2012
DOI:
10.1039/c2ib20164j
PubMed ID:
23042286
Type:
Article
ISSN:
1757-9694; 1757-9708
Sponsors:
The BBSRC/EPSRC for funding project number BB/D008522/1. This publication was based on work supported in part by Award No. KUK-C1-013-03, made by King Abdullah University of Science and Technology (KAUST).
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorKirkham, Glen R.en
dc.contributor.authorLovrics, Annaen
dc.contributor.authorByrne, Helen M.en
dc.contributor.authorJensen, Oliver E.en
dc.contributor.authorKing, John R.en
dc.contributor.authorShakesheff, Kevin M.en
dc.contributor.authorButtery, Lee D. K.en
dc.date.accessioned2016-02-25T13:11:37Zen
dc.date.available2016-02-25T13:11:37Zen
dc.date.issued2012en
dc.identifier.citationKirkham GR, Lovrics A, Byrne HM, Jensen OE, King JR, et al. (2012) Early gene regulation of osteogenesis in embryonic stem cells. Integrative Biology 4: 1470. Available: http://dx.doi.org/10.1039/c2ib20164j.en
dc.identifier.issn1757-9694en
dc.identifier.issn1757-9708en
dc.identifier.pmid23042286en
dc.identifier.doi10.1039/c2ib20164jen
dc.identifier.urihttp://hdl.handle.net/10754/598045en
dc.description.abstractThe 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.en
dc.description.sponsorshipThe BBSRC/EPSRC for funding project number BB/D008522/1. This publication was based on work supported in part by Award No. KUK-C1-013-03, made by King Abdullah University of Science and Technology (KAUST).en
dc.publisherRoyal Society of Chemistry (RSC)en
dc.titleEarly gene regulation of osteogenesis in embryonic stem cellsen
dc.typeArticleen
dc.identifier.journalIntegrative Biologyen
dc.contributor.institutionCentre for Biomolecular Sciences, Nottingham, United Kingdomen
dc.contributor.institutionUniversity of Nottingham, Nottingham, United Kingdomen
dc.contributor.institutionBiotalentum Ltd., Godollo, Hungaryen
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
kaust.grant.numberKUK-C1-013-03en

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