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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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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
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author 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
author_facet 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
author_sort Dittrich, Tobias
collection PubMed
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 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.
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spelling pubmed-97016082022-11-29 A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma 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 Cell Rep Methods Report 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. Elsevier 2022-11-01 /pmc/articles/PMC9701608/ /pubmed/36452870 http://dx.doi.org/10.1016/j.crmeth.2022.100322 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Report
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
A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title_full A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title_fullStr A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title_full_unstemmed A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title_short A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
title_sort high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma
topic Report
url 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
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