Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Knouse KA,Lopez KE,Bachofner M,Amon Adoi
10.1016/j.cell.2018.07.042subject
Has Abstractpub_date
2018-09-20 00:00:00pages
200-211.e13issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30970-Xjournal_volume
175pub_type
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