Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium

Sci Rep. 2016 Feb 26:6:21923. doi: 10.1038/srep21923.

Abstract

Using in-vivo lineage tracing data we quantified clonal expansion as well as proliferation and differentiation of the Lgr5-positive stem cell population in pyloric gastric glands. Fitting clone expansion models, we estimated that there are five effective Lgr5-positive cells able to give rise to monoclonal glands by replacing each other following a pattern of neutral drift dynamics. This analysis is instrumental to assess stem cell performance; however, stem cell proliferation is not quantified by clone expansion analysis. We identified a suitable mathematical model to quantify proliferation and differentiation of the Lgr5-positive population. As expected for populations in steady-state, the proliferation rate of the Lgr5-positive population was equal to its rate of differentiation. This rate was significantly faster than the rate at which effective cells are replaced, estimated by modelling clone expansion/contraction. This suggests that the majority of Lgr5-positive cell divisions serve to renew epithelial cells and only few result in the effective replacement of a neighbour to effect expansion to the entire gland. The application of the model under altered situations with uncoupled differentiation and proliferation was demonstrated. This methodology represents a valuable tool for quantifying stem cell performance in homeostasis and importantly for deciphering altered stem cell behaviour in disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation*
  • Epithelium / metabolism*
  • Epithelium / physiology
  • Mice
  • Models, Biological
  • Pylorus / metabolism*
  • Pylorus / physiology
  • Receptors, G-Protein-Coupled*
  • Stem Cells / metabolism*
  • Stem Cells / physiology

Substances

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