Journal article
Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation
AP Ng, M Kauppi, D Metcalf, CD Hyland, EC Josefsson, M Lebois, JG Zhang, TM Baldwin, L Di Rago, DJ Hilton, WS Alexander
Proceedings of the National Academy of Sciences of the United States of America | Published : 2014
Abstract
Thrombopoietin (TPO) acting via its receptor, the cellular homologue of the myeloproliferative leukemia virus oncogene (Mpl), is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO-dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets (MplPF4cre/PF4cre). Mpl PF4cre/PF4cre mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential progenitor cells, the latter displaying biological responses and a gene expression signature indicative of chronic TPO over..
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Awarded by Australian National Health and Medical Research Council
Awarded by Independent Research Institutes Infrastructure Support Scheme
Funding Acknowledgements
We thank Janelle Lochland, Jason Corbin, Emilia Simankowicz, Melanie Howell, Lauren Wilkins, and Keti Stoev for skilled assistance. This work was supported by Australian National Health and Medical Research Council Program Grants 1016647 and 490037; Fellowship 575501 (to W. S. A.); Independent Research Institutes Infrastructure Support Scheme Grant 361646; the Carden Fellowship of the Cancer Council, Victoria (to D. M.); the Cure Cancer Australia/Leukaemia Foundation Australia Post Doctoral Fellowship (to A.P.N.); Lions Fellowship, Cancer Council of Victoria (to A.P.N.); the Australian Cancer Research Fund; and Victorian State Government Operational Infrastructure Support.