Transcription profiling by array of mouse bone marrow lineage- c-Kit+ Sca-1+ cells in which floxed Mpl alleles were specifically and homozygously deleted in megakaryocytes and platelets

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 (MplPF4cre/PF4cre). MplPF4cre/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.

INSTRUMENT(S): MouseWG-6_V2_0_R1_11278593_A

ORGANISM(S): Mus musculus

SUBMITTER: Ashley Ng 

PROVIDER: E-MTAB-2389 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress