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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.<\/jats:p>","DOI":"10.1038\/srep21923","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T10:42:28Z","timestamp":1456483348000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium"],"prefix":"10.1038","volume":"6","author":[{"given":"Marc","family":"Leushacke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,26]]},"reference":[{"key":"BFsrep21923_CR1","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1038\/onc.2011.479","volume":"31","author":"M Leushacke","year":"2012","unstructured":"Leushacke, M. & Barker, N. Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer. Oncogene 31, 3009\u20133022, doi: 10.1038\/onc.2011.479 (2012).","journal-title":"Oncogene"},{"key":"BFsrep21923_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.stem.2009.11.013","volume":"6","author":"N Barker","year":"2010","unstructured":"Barker, N. et al. Lgr5(+ve) Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro. Cell Stem Cell 6, 25\u201336, doi: 10.1016\/j.stem.2009.11.013 (2010).","journal-title":"Cell Stem Cell"},{"key":"BFsrep21923_CR3","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.celrep.2013.09.025","volume":"5","author":"M Leushacke","year":"2013","unstructured":"Leushacke, M., Ng, A., Galle, J., Loeffler, M. & Barker, N. Lgr5(+) gastric stem cells divide symmetrically to effect epithelial homeostasis in the pylorus. 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