Mar 19, 2014

Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation

BioRxiv : the Preprint Server for Biology
Ashley P NgWarren S Alexander

Abstract

Thrombopoietin (TPO) acting via its receptor 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 ( Mpl PF4cre/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-stimulation as the underlying causative mechanism, despite a normal circulating TPO level. Thus, TPO signaling in megakaryocytes is dispensable for platelet production; its key role in control of platelet number is via generation and stimulation of the bipotential megakaryocyte precursors. Nevertheless, Mpl expression on megakaryocytes and platelets is essential to prevent megakaryocytosis and myeloproliferation by restricting the amount of TPO available to stimulate the production of megakaryocytes from the progenitor cell pool. Significance statement Blood platelets, the small circulating cells that co-ordi...Continue Reading

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Mentioned in this Paper

MRNA Maturation
Gene Editing
Megakaryocytes
Thrombopoiesis
Bone Marrow
TPO
Receptors, Cell Surface
Thrombopoietin-mediated Signaling Pathway
Gene Expression
Investigation of Megakaryocytes

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