Structural analysis of resting mouse platelets by 3D-EM reveals an unexpected variation in α-granule shape

Irina Pokrovskaya, Michael Tobin, Rohan Desai, Maria A. Aronova, Jeffrey A. Kamykowski, Guofeng Zhang, Smita Joshi, Sidney W. Whiteheart, Richard D. Leapman, Brian Storrie

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Pages (from-to)608-617
Number of pages10
JournalPlatelets
Volume32
Issue number5
DOIs
StatePublished - 2021

Bibliographical note

Publisher Copyright:
© 2020 Taylor & Francis Group, LLC.

Keywords

  • 3D SBF-SEM
  • electron microscopy
  • mouse
  • organelles
  • platelets
  • α-granules

ASJC Scopus subject areas

  • Hematology

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