Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium

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Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium
Title:
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium
Journal Title:
Scientific Reports
Keywords:
Publication Date:
26 February 2016
Citation:
Leushacke, M., Barker, N., and Pin, C. (2016). Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium. Sci. Rep. 6, 21923.
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This Research was supported by Core Funding from Agency for Science, Technology and Research (A*STAR) and the Singapore Gastric Cancer Consortium. Grant number is not applicable.
Description:
ISSN:
2045-2322
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