c-Myc–mediated control of cell fate in megakaryocyte-erythrocyte progenitors
| Autor: | Yinshi Guo, Wei Wei, Stephan W. Morris, Gladell P. Paner, Ameet R. Kini, Peter Breslin, Minghui Tang, Manuel O. Diaz, Jiwang Zhang, Patrick J. Stiff, Serhan Alkan, Shubin Zhang, Chao Niu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Blood Platelets
Erythrocytes Hematopoiesis and Stem Cells T-Lymphocytes Megakaryocyte Progenitor Cells Immunology Biology Biochemistry Thrombopoiesis Proto-Oncogene Proteins c-myc Mice Megakaryocyte Bone Marrow Erythrocyte differentiation medicine Animals Progenitor cell Erythroid Precursor Cells Cell Size Megakaryocytopoiesis Mice Knockout Thrombocytosis B-Lymphocytes Ploidies Macrophages Anemia Cell Differentiation Leukopenia Cell Biology Hematology Cell biology Haematopoiesis medicine.anatomical_structure Megakaryocytes Granulocytes |
| Zdroj: | Blood. 114:2097-2106 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-01-197947 |
| Popis: | It has been found that c-Myc protein plays a critical role in controlling self-renewal versus differentiation in hematopoietic stem cells. We report that c-Myc also controls the fate of megakaryocyte-erythrocyte progenitors through regulating the differentiation of erythroid and megakaryocytic progenitors. In addition to the significant reduction of granulocytes/macrophages and B and T lymphocytes because of the reduction of their corresponding progenitors, we found significantly increased numbers of megakaryocytic progenitors and mature megakaryocytes in bone marrow and spleens of c-Myc-knockout (c-Myc−/−) mice. Differentiation of erythrocytes was blocked at the erythroid progenitor stage. This increased megakaryocytopoiesis is a cell-intrinsic defect of c-Myc-mutant hematopoietic stem cells, as shown by transplantation studies. Furthermore, we found that c-Myc is required for polyploidy formation but not for cytoplasmic maturation of megakaryocytes. Megakaryocytes from c-Myc−/− mice are significantly smaller in size and lower in ploidy than those of control mice; however, because of the dramatic increase in megakaryocyte number, although fewer platelets are produced by each megakaryocyte, a greater than 3-fold increase in platelet number was consistently observed in c-Myc−/− mice. Thus, c-Myc−/− mice develop a syndrome of severe thrombocytosis-anemia-leukopenia because of significant increases in megakaryocytopoiesis and concomitant blockage of erythrocyte differentiation and reductions in myelolymphopoiesis. |
| Databáze: | OpenAIRE |
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