Mice serve as a crucial in vivo model for the study of platelet and megakaryocyte (Mk) biology. With the increasing prevalence of transgenic and knockout mice in research, a thorough understanding of the similarities and differences between murine and human platelet/Mk biology is essential. This study aims to provide a detailed comparison of the significant morphological differences between Mks, platelets, and the mechanisms of thrombopoiesis in both humans and mice.
This review examines the distinct structural and ultrastructural characteristics of both murine and human platelets and Mks. Immunoelectron microscopy was employed to localize several platelet and Mk glycoproteins in murine cells using polyclonal antibodies against human platelet proteins. These findings were then compared with existing data on human cells. Furthermore, a detailed examination of the ultrastructure of maturing murine and human Mks in both culture and bone marrow was conducted to facilitate a direct comparison of platelet production under both in vivo and in vitro conditions.
The morphological analysis reveals well-established and significant differences between human and murine platelets. Notably, murine platelets are smaller in size and present in greater numbers compared to human platelets. They also exhibit a more pronounced heterogeneity in granule composition. Immunoelectron microscopy further revealed a high degree of compartmentalization within murine platelet alpha-granules. Remarkably, these murine alpha-granules share similarities with their human counterparts, demonstrating an asymmetrical distribution of von Willebrand factor (vWF), and the presence of alpha(IIb)beta(3) and P-selectin (CD62P) labeling within the granule limiting membrane. Another key difference observed in vivo is the consistent localization of murine Mks within the spleen, a feature not typically seen in humans. This study also presents, for the first time, the subcellular processes involved in platelet formation and release by murine Mks, offering a valuable comparison to the mechanisms observed in humans. Consistent variations were identified in the redistribution pathway of demarcation membranes preceding platelet formation, potentially offering critical insights into the mechanisms underlying platelet release.
In conclusion, while human and murine platelets and Mks exhibit several notable ultrastructural differences – including size, quantity, histological distribution, and platelet shedding mechanisms – which have been highlighted and analyzed in this report, the significant similarities in organelle and glycoprotein subcellular distribution underscore the value of mice as an excellent in vivo model for investigating various facets of human Mk and platelet biology. These comparative insights are critical for accurately interpreting data from murine models and applying these findings to human health research.
