Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling

• Published in: Scientific reports Vol. 7; no. 1; pp. 14953 - 10
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-11-2017; Nature Publishing Group
• Subjects: 13/2; 13/21; 13/31; 38; 38/61; 631/67/1990/291; 631/80; 64/60; 82/80; Animal models; ates of america; Bone marrow; bone-marrow microenvironment; c-Kit protein; c-mpl; Cell and Molecular Biology; Cell Biology; Cell cycle; Cell- och molekylärbiologi; Cellbiologi; deficiencies; expression; G1 phase; Hematopoietic stem cells; Humanities and Social Sciences; Lymphocytes; Lymphocytes B; Lymphoid cells; Lymphopoiesis; multidisciplinary; multipotent progenitors; myc; Myc protein; p21689; Peripheral blood; platelets; Progenitor cells; receptor mpl; Science; Science & Technology - Other Topics; Science (multidisciplinary); Spleen; Stem cells; Thrombopoietin; transgenic mice; v107
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15023-2

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.