Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/123297
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling
Author: Au, A.
Lebois, M.
Sim, S.
Cannon, P.
Corbin, J.
Gangatirkar, P.
Hyland, C.
Moujalled, D.
Rutgersson, A.
Yassinson, F.
Kile, B.
Mason, K.
Ng, A.
Alexander, W.
Josefsson, E.
Citation: Scientific Reports, 2017; 7(1):14953-1-14953-10
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Amanda E. Au, Marion Lebois, Starling A. Sim, Ping Cannon, Jason Corbin, Pradnya Gangatirkar, Craig D. Hyland, Diane Moujalled, Angelika Rutgersson, Fatme Yassinson, Benjamin T. Kile, Kylie D. Mason, Ashley P. Ng, Warren S. Alexander, Emma C. Josefsson
Abstract: Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo -/- mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl -/- mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1+c-Kit+ (LSK) cells and an increase in CLP formation. Moreover, Mpl -/- mice exhibited increased numbers of PreB2 and immature B-cells in bone marrow and spleen, with an increased proportion of B-lymphoid cells in the G1 phase of the cell cycle. Conversely, elevated TPO signaling in Tpo Tg mice was associated with reduced B-lymphopoiesis. Although at steady state, peripheral blood lymphocyte counts were normal in both models, Mpl -/- Eµ-myc mice showed an enhanced preneoplastic phase with increased numbers of splenic PreB2 and immature B-cells, a reduced quiescent fraction, and augmented blood lymphocyte counts. Thus, although Mpl is not expressed on lymphoid cells, TPO signaling may indirectly influence B-lymphopoiesis and the preneoplastic state in Myc-driven B-cell lymphomagenesis by lineage priming in multipotential progenitor cells.
Keywords: B-Lymphocytes
Description: Published online: 02 November 2017
Rights: © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 1000001805
DOI: 10.1038/s41598-017-15023-2
Grant ID: http://purl.org/au-research/grants/nhmrc/1079250
http://purl.org/au-research/grants/nhmrc/1060179
http://purl.org/au-research/grants/nhmrc/1016647
http://purl.org/au-research/grants/nhmrc/1058344
http://purl.org/au-research/grants/nhmrc/1063008
http://purl.org/au-research/grants/nhmrc/1090500
Appears in Collections:Medicine publications

Files in This Item:
File Description SizeFormat 
hdl_123297.pdfPublished version2.62 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.