Lgr5(+) gastric stem cells divide symmetrically to effect epithelial homeostasis in the pylorus

Cell Rep. 2013 Oct 31;5(2):349-56. doi: 10.1016/j.celrep.2013.09.025.

Abstract

The pyloric epithelium continuously self-renews throughout life, driven by limited reservoirs of resident Lgr5+ adult stem cells. Here, we characterize the population dynamics of these stem cells during epithelial homeostasis. Using a clonal fate-mapping strategy, we demonstrate that multiple Lgr5+ cells routinely contribute to epithelial renewal in the pyloric gland and, similar to what was previously observed in the intestine, a balanced homeostasis of the glandular epithelium and stem cell pools is predominantly achieved via neutral competition between symmetrically dividing Lgr5+ stem cells. Additionally, we document a lateral expansion of stem cell clones via gland fission under nondamage conditions. These findings represent a major advance in our basic understanding of tissue homeostasis in the stomach and form the foundation for identifying altered stem cell behavior during gastric disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Animals
  • Cell Lineage
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Homeostasis
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Pylorus / cytology*
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled