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A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma

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 a...

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Detalles Bibliográficos
Autores principales: Dittrich, Tobias, Köhrer, Sebastian, Schorb, Martin, Haberbosch, Isabella, Börmel, Mandy, Goldschmidt, Hartmut, Pajor, Gabor, Müller-Tidow, Carsten, Raab, Marc S., Hegenbart, Ute, Schönland, Stefan O., Schwab, Yannick, Krämer, Alwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701608/
https://www.ncbi.nlm.nih.gov/pubmed/36452870
http://dx.doi.org/10.1016/j.crmeth.2022.100322
Descripción
Sumario: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(pos) plasma cells from one patient with relapsed/refractory multiple myeloma and CD138(neg) 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.