Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture.

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

Cell

journal_title

Cell

authors

Knouse KA,Lopez KE,Bachofner M,Amon A

doi

10.1016/j.cell.2018.07.042

subject

Has Abstract

pub_date

2018-09-20 00:00:00

pages

200-211.e13

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(18)30970-X

journal_volume

175

pub_type

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