Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis

Abstract Megakaryocytopoiesis 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...

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Autores principales:	Lee Butcher, Maninder Ahluwalia, Tiit Örd, Jessica Johnston, Roger H. Morris, Endre Kiss-Toth, Tõnis Örd, Jorge D. Erusalimsky
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5476fb0e1b1f4ccab77aedb1a89886b2
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spelling	oai:doaj.org-article:5476fb0e1b1f4ccab77aedb1a89886b22021-12-02T11:53:09ZEvidence for a role of TRIB3 in the regulation of megakaryocytopoiesis10.1038/s41598-017-07096-w2045-2322https://doaj.org/article/5476fb0e1b1f4ccab77aedb1a89886b22017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07096-whttps://doaj.org/toc/2045-2322Abstract Megakaryocytopoiesis 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.Lee ButcherManinder AhluwaliaTiit ÖrdJessica JohnstonRoger H. MorrisEndre Kiss-TothTõnis ÖrdJorge D. ErusalimskyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lee Butcher Maninder Ahluwalia Tiit Örd Jessica Johnston Roger H. Morris Endre Kiss-Toth Tõnis Örd Jorge D. Erusalimsky Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
description	Abstract Megakaryocytopoiesis 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.
format	article
author	Lee Butcher Maninder Ahluwalia Tiit Örd Jessica Johnston Roger H. Morris Endre Kiss-Toth Tõnis Örd Jorge D. Erusalimsky
author_facet	Lee Butcher Maninder Ahluwalia Tiit Örd Jessica Johnston Roger H. Morris Endre Kiss-Toth Tõnis Örd Jorge D. Erusalimsky
author_sort	Lee Butcher
title	Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
title_short	Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
title_full	Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
title_fullStr	Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
title_full_unstemmed	Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
title_sort	evidence for a role of trib3 in the regulation of megakaryocytopoiesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5476fb0e1b1f4ccab77aedb1a89886b2
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Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis

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