title: Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium.
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.
authors.affiliation: A*STAR Institute of Medical Biology, Singapore.
authors.forename: Marc
authors.initials: M
authors.lastname: Leushacke
authors.affiliation: A*STAR Institute of Medical Biology, Singapore.|Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.affiliation: Gut Health and Food Safety Programme. Institute of Food Research, Norwich, UK.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D011708:Pylorus / Q000378:metabolism* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled