Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture.
Cell
; 175(1): 200-211.e13, 2018 09 20.
Article
em En
| MEDLINE
| ID: mdl-30146160
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Segregação de Cromossomos
/
Instabilidade Cromossômica
/
Epitélio
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article