Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium
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 mono...
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| Format: | Online |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768140/ |
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pubmed-47681402016-03-02 Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium Leushacke, Marc Barker, Nick Pin, Carmen Article 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. Nature Publishing Group 2016-02-26 /pmc/articles/PMC4768140/ /pubmed/26916214 http://dx.doi.org/10.1038/srep21923 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Leushacke, Marc Barker, Nick Pin, Carmen |
| spellingShingle |
Leushacke, Marc Barker, Nick Pin, Carmen Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| author_facet |
Leushacke, Marc Barker, Nick Pin, Carmen |
| author_sort |
Leushacke, Marc |
| title |
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| title_short |
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| title_full |
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| title_fullStr |
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| title_full_unstemmed |
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium |
| title_sort |
quantifying lgr5-positive stem cell behaviour in the pyloric epithelium |
| description |
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. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768140/ |
| _version_ |
1613543591816200192 |