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
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2017
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 mar..View full abstract
Awarded by Australian National Health and Medical Research Council
Awarded by Independent Research Institutes Infrastructure Support Scheme Grant
The authors thank J. McManus, J. Lochland, S. Lee, L. Cengia, L. Di Rago, K. Stoev and S. Ross for outstanding assistance. This work was supported by grant funds received from the following: Leukaemia Foundation Australia Grant-in-Aid (E.C.J., K.D.M.), Sir Edward Dunlop Medical Research Foundation (E.C.J.), the Australian National Health and Medical Research Council Project Grant (E.C.J. 1079250, A.P.N. 1060179), Program Grant (1016647), Fellowships (W.S.A. 1058344; B.T.K. 1063008; K.D.M. 1090500) and Independent Research Institutes Infrastructure Support Scheme Grant (9000220) and a Victorian State Government Operational Infrastructure Support Grant. E.C.J. is the recipient of a fellowship from the Lorenzo and Pamela Galli Charitable Trust.