A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed-refractory multiple myeloma
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ABSTRACT:
SUBMITTER: Alwin Krämer
PROVIDER: EMPIAR-11243 | biostudies-other |
REPOSITORIES: biostudies-other
Publications
A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma.
Dittrich Tobias T Köhrer Sebastian S Schorb Martin M Haberbosch Isabella I Börmel Mandy M Goldschmidt Hartmut H Pajor Gabor G Müller-Tidow Carsten C Raab Marc S MS Hegenbart Ute U Schönland Stefan O SO Schwab Yannick Y Krämer Alwin A
Cell reports methods 20221101 11
Electron microscopy is the gold standard to characterize centrosomal ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. We therefore developed a generalizable, semi-automated high-throughput electron tomography strategy to study centrosome aberrations in sparse patient-derived cancer cells at nanoscale. As proof of principle, we present electron tomography data on 455 centrioles of CD138<sup>pos</sup> plasma cells from one patient with r ...[more]
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Project description:Electron microscopy is the gold standard to characterize centrosomal ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. We therefore developed a generalizable, semi-automated high-throughput electron tomography strategy to study centrosome aberrations in sparse patient-derived cancer cells at nanoscale. As proof of principle, we present electron tomography data on 455 centrioles of CD138pos plasma cells from one patient with relapsed/refractory multiple myeloma and CD138neg bone marrow mononuclear cells from three healthy donors as a control. Plasma cells from the myeloma patient displayed 122 over-elongated centrioles (48.8%). Particularly mother centrioles also harbored gross structural abnormalities, including fragmentation and disturbed microtubule cylinder formation, while control centrioles were phenotypically unremarkable. These data demonstrate the feasibility of our scalable high-throughput electron tomography strategy to study structural centrosome aberrations in primary tumor cells. Moreover, our electron tomography workflow and data provide a resource for the characterization of cell organelles beyond centrosomes.
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Project description:Electron microscopy is the gold standard to characterize cellular ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. Here, we describe a semi-automated high-throughput strategy using single-axis serial section electron tomography to investigate and analyze centriole ultrastructure in bone-marrow-derived, primary human CD138pos plasma cells. The protocol comprises steps for electron microscopy sample preparation, semi-automated transmission electron microscopy screening, and screening evaluation for cells of interest. Thereafter, we detail tomography acquisition, data reconstruction, and joining. For complete details on the use and execution of this protocol, please refer to Dittrich et al.1.
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