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dc.contributor.authorButcher, Lee
dc.contributor.authorAhluwalia, Maninder
dc.contributor.authorÖrd, Tiit
dc.contributor.authorJohnston, Jessica
dc.contributor.authorMorris, Keith
dc.contributor.authorKiss-Toth, Endre
dc.contributor.authorÖrd, Tõnis
dc.contributor.authorErusalimsky, Jorge
dc.date.accessioned2017-09-07T10:53:48Z
dc.date.available2017-09-07T10:53:48Z
dc.date.issued2017-07-27
dc.identifier.citationButcher, L., Ahluwalia, M., Örd, T., Johnston, J., Morris, R.H., Kiss-Toth, E., Örd, T. and Erusalimsky, J.D. (2017) 'Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis', Scientific Reports, 7.en_US
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322 (ESSN)
dc.identifier.urihttp://hdl.handle.net/10369/8762
dc.descriptionThis article was published in Scientific Reports on 27 July 2017 available open access at http://dx.doi.org/10.1038/s41598-017-07096-wen_US
dc.description.abstractMegakaryocytopoiesis is a complex differentiation process driven by the hormone thrombopoietin by which haematopoietic progenitor cells give rise to megakaryocytes, the giant bone marrow cells that in turn break down to form blood platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein increasingly implicated in the regulation of cellular differentiation programmes. Previous studies have hinted that TRIB3 could be also involved in megakaryocytopoiesis but its role in this process has so far not been investigated. Using cellular model systems of haematopoietic lineage differentiation here we demonstrate that TRIB3 is a negative modulator of megakaryocytopoiesis. We found that in primary cultures derived from human haematopoietic progenitor cells, thrombopoietin-induced megakaryocytic differentiation led to a time and dose-dependent decrease in TRIB3 mRNA levels. In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte antigen expression, as well as basal levels of ERK1/2 phosphorylation. In primary haematopoietic cell cultures, silencing of TRIB3 facilitated megakaryocyte differentiation. In contrast, over-expression of TRIB3 in these cells inhibited the differentiation process. The in-vitro identification of TRIB3 as a negative regulator of megakaryocytopoiesis suggests that in-vivo this gene could be important for the regulation of platelet production.en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofseriesScientific Reports;
dc.titleEvidence for a role of TRIB3 in the regulation of megakaryocytopoiesisen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-017-07096-w
dcterms.dateAccepted2017-06-27
rioxxterms.funderCardiff Metropolitan Universityen_US
rioxxterms.identifier.projectCardiff Metropolian (Internal)en_US
rioxxterms.versionVoRen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/en_US
rioxxterms.licenseref.startdate2017-09-07
dc.refexceptionOA compliant
rioxxterms.funder.project37baf166-7129-4cd4-b6a1-507454d1372een_US


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