Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling

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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number14953
Number of pages10
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • cell biology
  • lymphoma

Cite this

Au, A. E., Lebois, M., Sim, S. A., Cannon, P., Corbin, J., Gangatirkar, P., ... Josefsson, E. C. (2017). Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling. Scientific Reports, 7(1), [14953]. https://doi.org/10.1038/s41598-017-15023-2
Au, Amanda E. ; Lebois, Marion ; Sim, Starling A. ; Cannon, Ping ; Corbin, Jason ; Gangatirkar, Pradnya ; Hyland, Craig D. ; Moujalled, Diane ; Rutgersson, Angelika ; Yassinson, Fatme ; Kile, Benjamin T. ; Mason, Kylie D. ; Ng, Ashley P. ; Alexander, Warren S. ; Josefsson, Emma C. / Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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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.",
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author = "Au, {Amanda E.} and Marion Lebois and Sim, {Starling A.} and Ping Cannon and Jason Corbin and Pradnya Gangatirkar and Hyland, {Craig D.} and Diane Moujalled and Angelika Rutgersson and Fatme Yassinson and Kile, {Benjamin T.} and Mason, {Kylie D.} and Ng, {Ashley P.} and Alexander, {Warren S.} and Josefsson, {Emma C.}",
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Au, AE, Lebois, M, Sim, SA, Cannon, P, Corbin, J, Gangatirkar, P, Hyland, CD, Moujalled, D, Rutgersson, A, Yassinson, F, Kile, BT, Mason, KD, Ng, AP, Alexander, WS & Josefsson, EC 2017, 'Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling' Scientific Reports, vol. 7, no. 1, 14953. https://doi.org/10.1038/s41598-017-15023-2

Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling. / Au, Amanda E.; Lebois, Marion; Sim, Starling A.; Cannon, Ping; Corbin, Jason; Gangatirkar, Pradnya; Hyland, Craig D.; Moujalled, Diane; Rutgersson, Angelika; Yassinson, Fatme; Kile, Benjamin T.; Mason, Kylie D.; Ng, Ashley P.; Alexander, Warren S.; Josefsson, Emma C.

In: Scientific Reports, Vol. 7, No. 1, 14953, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling

AU - Au, Amanda E.

AU - Lebois, Marion

AU - Sim, Starling A.

AU - Cannon, Ping

AU - Corbin, Jason

AU - Gangatirkar, Pradnya

AU - Hyland, Craig D.

AU - Moujalled, Diane

AU - Rutgersson, Angelika

AU - Yassinson, Fatme

AU - Kile, Benjamin T.

AU - Mason, Kylie D.

AU - Ng, Ashley P.

AU - Alexander, Warren S.

AU - Josefsson, Emma C.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - cell biology

KW - lymphoma

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JF - Scientific Reports

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Au AE, Lebois M, Sim SA, Cannon P, Corbin J, Gangatirkar P et al. Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling. Scientific Reports. 2017 Dec 1;7(1). 14953. https://doi.org/10.1038/s41598-017-15023-2