Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes

EMBO J. 2011 Mar 16;30(6):1104-9. doi: 10.1038/emboj.2011.26. Epub 2011 Feb 4.

Abstract

Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse, yet divide every day. We now demonstrate biochemically that primary isolated Lgr5+ve stem cells contain significant telomerase activity. Telomerase activity rapidly decreases in the undifferentiated progeny of these stem cells and is entirely lost in differentiated villus cells. Conversely, asymmetric segregation of chromosomes has been proposed as a mechanism for stem cells to protect their genomes against damage. We determined the average cell cycle length of Lgr5+ve stem cells at 21.5 h and find that Lgr5+ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Chromosome Segregation*
  • Epithelial Cells / enzymology
  • Epithelial Cells / physiology
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / enzymology*
  • Mice
  • Stem Cell Niche*
  • Stem Cells / enzymology*
  • Stem Cells / physiology*
  • Telomerase / metabolism*
  • Time Factors

Substances

  • Telomerase