Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture
Much of our understanding of chromosome segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for chromosome segregation by comparing chromosome segregation fidelity across several primary cell types in native and nonnative contexts. We discover that...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125270 |
| _version_ | 1826204397954138112 |
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| author | Knouse, Kristin Ann Bachofner, Marc Amon, Angelika B Lopez-Bernal, Kristina Elizabeth, 1980- |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Knouse, Kristin Ann Bachofner, Marc Amon, Angelika B Lopez-Bernal, Kristina Elizabeth, 1980- |
| author_sort | Knouse, Kristin Ann |
| collection | MIT |
| description | Much of our understanding of chromosome segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for chromosome segregation by comparing chromosome segregation fidelity across several primary cell types in native and nonnative contexts. We discover that epithelial cells have increased chromosome missegregation outside of their native tissues. Using organoid culture systems, we show that tissue architecture, specifically integrin function, is required for accurate chromosome segregation. We find that tissue architecture enhances the correction of merotelic microtubule-kinetochore attachments, and this is especially important for maintaining chromosome stability in the polyploid liver. We propose that disruption of tissue architecture could underlie the widespread chromosome instability across epithelial cancers. Moreover, our findings highlight the extent to which extracellular context can influence intrinsic cellular processes and the limitations of cell culture systems for studying cells that naturally function within a tissue. Tissue architecture and integrin function are critical factors that support chromosome segregation fidelity in epithelial tissues. |
| first_indexed | 2024-09-23T12:54:26Z |
| format | Article |
| id | mit-1721.1/125270 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:54:26Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1252702022-10-01T11:48:08Z Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture Knouse, Kristin Ann Bachofner, Marc Amon, Angelika B Lopez-Bernal, Kristina Elizabeth, 1980- Koch Institute for Integrative Cancer Research at MIT Much of our understanding of chromosome segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for chromosome segregation by comparing chromosome segregation fidelity across several primary cell types in native and nonnative contexts. We discover that epithelial cells have increased chromosome missegregation outside of their native tissues. Using organoid culture systems, we show that tissue architecture, specifically integrin function, is required for accurate chromosome segregation. We find that tissue architecture enhances the correction of merotelic microtubule-kinetochore attachments, and this is especially important for maintaining chromosome stability in the polyploid liver. We propose that disruption of tissue architecture could underlie the widespread chromosome instability across epithelial cancers. Moreover, our findings highlight the extent to which extracellular context can influence intrinsic cellular processes and the limitations of cell culture systems for studying cells that naturally function within a tissue. Tissue architecture and integrin function are critical factors that support chromosome segregation fidelity in epithelial tissues. National Institutes of Health (Grant CA206157–22) National Institute of General Medical Sciences (NIGMS) (Grant T32GM007753) 2020-05-15T16:10:51Z 2020-05-15T16:10:51Z 2018-08 2018-05 2019-11-26T14:28:35Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 https://hdl.handle.net/1721.1/125270 Knouse, Kristin A. et al. "Chromosome segregation fidelity in epithelia requires tissue architecture." Cell 175, 1 (September 2018): P200-211.e13 © 2018 Elsevier Inc en http://dx.doi.org/10.1016/j.cell.2018.07.042 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Knouse, Kristin Ann Bachofner, Marc Amon, Angelika B Lopez-Bernal, Kristina Elizabeth, 1980- Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title | Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title_full | Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title_fullStr | Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title_full_unstemmed | Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title_short | Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture |
| title_sort | chromosome segregation fidelity in epithelia requires tissue architecture |
| url | https://hdl.handle.net/1721.1/125270 |
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