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Megakaryocytopoiesis and granulopoiesis in W/Wv mice: comparisons between bone marrow and spleen
S R Petursson1, P A Chervenick
1Department of Medicine, University of Pittsburgh School of Medicine, PA 15261.
Abstract:
To determine how megakaryocyte progenitor cells (CFU-M) of W/Wv mice are affected by the hematopoietic stem cell abnormality, megakaryocytopoiesis was studied in the spleen and marrow of these genetically anemic W/Wv mice. CFU-M were assayed in the soft gel colony-forming system. Megakaryocyte colony size was determined by counting the number of megakaryocytes per colony, and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cell preparations with use of an eyepiece micrometer. In spite of normal blood platelet levels, megakaryocyte level was reduced in the spleen and humerus to about 60% that of +/+ littermates. Megakaryocyte diameters were increased in W/Wv mice. CFU-M in W/Wv mice were reduced to 40% the number seen in the spleen of +/+ mice and to 62% in the humerus. In cell cycle studies, significantly fewer marrow CFU-M were in DNA synthesis in W/Wv mice compared with +/+ animals, but similar numbers of cells were in cycle in the spleen for both genotypes. No difference was observed between W/Wv and +/+ CFU-M in their requirement for exogenous colony-stimulating activity or in the distribution of colony sizes. However, CFU-M-derived colonies cloned from adherent cell-depleted marrow cells were significantly smaller compared with those cultured from unfractionated marrow cells. Results for granulocytes and granulocyte-macrophage progenitor cells (CFU-GM) were similar to those obtained for the megakaryocyte series, indicating that the abnormalities are present in different cell lineages. These results suggest that the macromegakaryocytosis of W/Wv mice appears to be a compensation for the megakaryocytopenia. Cells in the progenitor cell compartment appeared not to be involved in this compensation. Furthermore, adherent cells appear to elaborate a factor regulating megakaryocyte development. These findings are compatible with two-level regulation of megakaryocyte formation and a complex mechanism of blood platelet level regulation.
Insights
W/Wv mice exhibit reduced megakaryocyte progenitor cells (CFU-M) and macromegakaryocytosis, suggesting compensation for megakaryocytopenia. Adherent cells may regulate megakaryocyte development, impacting platelet regulation.
Area of Science:
- Hematology
- Stem Cell Biology
- Genetics
Background:
- W/Wv mice possess a hematopoietic stem cell abnormality.
- Megakaryocytopoiesis, the production of megakaryocytes, is crucial for platelet formation.
- Understanding progenitor cell behavior is key to deciphering hematopoietic regulation.
Purpose of the Study:
- To investigate the impact of hematopoietic stem cell abnormality on megakaryocyte progenitor cells (CFU-M) in W/Wv mice.
- To analyze megakaryocytopoiesis in the spleen and marrow of genetically anemic W/Wv mice.
- To explore the regulatory mechanisms of megakaryocyte development and platelet production.
Main Methods:
- Assaying CFU-M using a soft gel colony-forming system.
- Measuring megakaryocyte colony size and diameter.
- Conducting cell cycle studies and analyzing progenitor cell requirements for colony-stimulating activity.
Main Results:
- W/Wv mice showed reduced megakaryocyte levels and increased megakaryocyte diameters compared to +/+ littermates.
- CFU-M numbers were significantly reduced in W/Wv mice spleen and humerus.
- Abnormalities were observed in granulocytes and granulocyte-macrophage progenitor cells (CFU-GM) as well, indicating multi-lineage effects.
Conclusions:
- Macromegakaryocytosis in W/Wv mice appears compensatory for megakaryocytopenia.
- Progenitor cell compartment was not involved in this compensation.
- Adherent cells may produce a factor regulating megakaryocyte development, suggesting a complex, two-level regulation of megakaryocyte formation and platelet levels.
