Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture

Cell. 2018 Sep 20;175(1):200-211.e13. doi: 10.1016/j.cell.2018.07.042. Epub 2018 Aug 23.


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.

Keywords: aneuploidy; chromosome segregation; integrin; tissue architecture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Aggregation / physiology
  • Cell Culture Techniques / methods
  • Chromosomal Instability / physiology*
  • Chromosome Segregation / physiology*
  • Chromosomes / physiology
  • Epithelial Cells / physiology
  • Epithelium / physiology*
  • Female
  • Kinetochores / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / metabolism
  • Mitosis
  • Organoids / physiology
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology