Structural analysis of resting mouse platelets by 3D-EM reveals an unexpected variation in α-granule shape. (4th July 2021)

• Record Type: Journal Article
• Authors: Pokrovskaya, Irina; Tobin, Michael; Desai, Rohan; Aronova, Maria A.; Kamykowski, Jeffrey A.; Zhang, Guofeng; Joshi, Smita; Whiteheart, Sidney W.; Leapman, Richard D.; Storrie, Brian
• Is Part Of: Platelets. Volume 32:Number 5(2021)
• Page Start: 608
• Page End: 617
• Publication Date: 2021-07-04
• Subjects: 3D SBF-SEM -- electron microscopy -- mouse -- organelles -- platelets -- α-granules; Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• DOI: 10.1080/09537104.2020.1799970
• Languages: English
• ISSNs: 0953-7104

Abstract

Abstract: Mice and mouse platelets are major experimental models for hemostasis and thrombosis; however, important physiological data from this model has received little to no quantitative, 3D ultrastructural analysis. We used state-of-the-art, serial block imaging scanning electron microscopy (SBF-SEM, nominal Z-step size was 35 nm) to image resting platelets from C57BL/6 mice. α-Granules were identified morphologically and rendered in 3D space. The quantitative analysis revealed that mouse α-granules typically had a variable, elongated, rod shape, different from the round/ovoid shape of human α–granules. This variation in length was confirmed qualitatively by higher-resolution, focused ion beam (FIB) SEM at a nominal 5 nm Z-step size. The unexpected α-granule shape raises novel questions regarding α-granule biogenesis and dynamics. Does the variation arise at the level of the megakaryocyte and α-granule biogenesis or from differences in α-granule dynamics and organelle fusion/fission events within circulating platelets? Further quantitative analysis revealed that the two major organelles in circulating platelets, α-granules and mitochondria, displayed a stronger linear relationship between organelle number/volume and platelet size, i.e., a scaling in number and volume to platelet size, than found in human platelets suggestive of a tighter mechanistic regulation of their inclusion during platelet biogenesis. In conclusion, the overall spatial arrangement of organelles within mouse platelets was similar to that of resting human platelets, with mouse α-granules clustered closely together with little space for interdigitation of other organelles.