Proceedings of the National Academy of Sciences - PNAS, 2014-04, Vol.111 (16), p.5884-5889
2014
Details
- Autor(en) / Beteiligte
- Titel
- Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2014-04, Vol.111 (16), p.5884-5889
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 (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 overstimulation 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1404354111Titel-ID: cdi_crossref_primary_10_1073_pnas_1404354111
- Format
- –
- Schlagworte
- Animals, Antigens, CD34 - metabolism, Biological Sciences, Blood, Blood platelets, Blood Platelets - cytology, Blood Platelets - metabolism, Bone marrow, Bone marrow cells, Cell Compartmentation, Cell Proliferation, Cells, Clone Cells, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Gene Targeting, Genetic Loci - genetics, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - metabolism, Integrases - metabolism, Megakaryocytes, Megakaryocytes - cytology, Megakaryocytes - metabolism, Mice, Models, Biological, Myeloid Cells - cytology, Myeloid Cells - metabolism, Platelets, Progenitor cells, Receptors, Thrombopoietin - metabolism, Signatures, Stem cells, Thrombocytosis, Thrombopoiesis, Thrombopoietin - genetics, Thrombopoietin - metabolism, Transcription, Genetic