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Of mice and men: comparison of the ultrastructure of megakaryocytes and platelets
A Schmitt1, J Guichard, J M Massé
1INSERM U.474, Institut Cochin de Génétique Moléculaire, Hôpital de Port-Royal, 123, Boulevard de Port-Royal, 75014 Paris, France.
Objective:
Mice provide an excellent model for studying platelet and megakaryocyte (Mk) biology in vivo. Given the increasing use of transgenic and knockout mice, it is important that any similarities and differences between murine and human platelet/Mk biology be well defined. Therefore the objective of this study was to compare and contrast in detail any significant morphological differences between Mks, platelets, and mechanisms of thrombopoiesis in humans and mice.
Methods:
The distinctive structural and ultrastructural features of murine and human platelets and Mks are reviewed. Several platelet and Mk glycoproteins were also localized in murine cells by immunoelectron microscopy using polyclonal antibodies directed against human platelet proteins and compared to existing human data. Finally, the ultrastructure of maturing murine and human Mks in culture and bone marrow were examined in detail to facilitate a comparison of either in vivo or in vitro platelet production.
Results:
Human and murine platelets exhibit significant but well-established morphological differences. Murine platelets are smaller and more numerous and display much greater granule heterogeneity than their human counterparts. Immunoelectron microscopy also demonstrated that murine platelet alpha-granules are highly compartmentalized. In fact, they are remarkably similar to human alpha-granules, with asymmetrical distribution of von Willebrand factor (vWF), and labeling of alpha(IIb)beta(3) and P-selectin (CD62P) in the granule limiting membrane. In vivo, murine but not human Mks are also consistently localized within the spleen. Subcellular events accompanying platelet formation and release by murine Mks are presented for the first time, and compared to human. Consistent differences were found in the pathway of redistribution of demarcation membranes preceding platelet formation, which may be important for the clarification of the mechanism of platelet release.
Conclusion:
Human and murine platelets and Mks display several characteristic ultrastructural differences (size, number, histological distribution, platelet shedding) which have been emphasized and analyzed in this report. Nevertheless, since there are also many close similarities (organelle and glycoprotein subcellular distribution) mice offer an excellent in vivo model to study various aspects of human Mk and platelet biology.
Insights
Mice and human platelets and megakaryocytes (Mks) show distinct ultrastructural differences in size, number, and distribution. Despite these variations, mice remain a valuable in vivo model for studying human Mk and platelet biology due to conserved similarities.
Area of Science:
- Hematology
- Cell Biology
- Comparative Biology
Background:
- Mice are widely used models for studying platelet and megakaryocyte (Mk) biology.
- Understanding similarities and differences between murine and human systems is crucial for accurate research.
- Transgenic and knockout mouse models are increasingly utilized in this field.
Purpose of the Study:
- To conduct a detailed comparison of morphological differences between murine and human Mks and platelets.
- To analyze the mechanisms of thrombopoiesis in both species.
- To evaluate the suitability of mice as a model for human platelet and Mk research.
Main Methods:
- Review of distinctive structural and ultrastructural features of murine and human platelets and Mks.
- Immunoelectron microscopy to localize platelet and Mk glycoproteins in murine cells.
- Detailed examination of maturing Mks in culture and bone marrow for comparative analysis of platelet production.
Main Results:
- Murine platelets are smaller, more numerous, and exhibit greater granule heterogeneity than human platelets.
- Murine platelet alpha-granules are highly compartmentalized, similar to human counterparts, with conserved glycoprotein distribution.
- Distinct differences were observed in demarcation membrane redistribution during platelet formation in mice compared to humans.
- Murine Mks are consistently found in the spleen in vivo, unlike human Mks.
Conclusions:
- Significant ultrastructural differences exist between human and murine platelets and Mks, including size, number, distribution, and platelet shedding.
- Close similarities in organelle and glycoprotein distribution highlight the value of mice as an in vivo model.
- Mice offer a robust model for investigating various aspects of human Mk and platelet biology.
