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The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns
The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell–niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cel...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808490/ https://www.ncbi.nlm.nih.gov/pubmed/17335343 http://dx.doi.org/10.1371/journal.pcbi.0030028 |
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author | Nicolas, Pierre Kim, Kyoung-Mee Shibata, Darryl Tavaré, Simon |
author_facet | Nicolas, Pierre Kim, Kyoung-Mee Shibata, Darryl Tavaré, Simon |
author_sort | Nicolas, Pierre |
collection | PubMed |
description | The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell–niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche and the niche succession time, the methylation/demethylation process, and the randomness due to sampling. As a consequence, methylation pattern studies can reveal niche characteristics but also require appropriate statistical methods. The analysis of methylation patterns sampled from colon crypts is a prototype of such a study. Previous analyses were based on forward simulation of the cell content of the whole crypt and subsequent comparisons between simulated and experimental data using a few statistics as a proxy to summarize the data. In this paper we develop a more powerful method to analyze these data based on coalescent modelling and Bayesian inference. Results support a scenario where the colon crypt is maintained by a high number of stem cells; the posterior indicates a number greater than eight and the posterior mode is between 15 and 20. The results also provide further evidence for synergistic effects in the methylation/demethylation process that could for the first time be quantitatively assessed through their long-term consequences such as the coexistence of hypermethylated and hypomethylated patterns in the same colon crypt. |
format | Text |
id | pubmed-1808490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-18084902007-03-03 The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns Nicolas, Pierre Kim, Kyoung-Mee Shibata, Darryl Tavaré, Simon PLoS Comput Biol Research Article The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell–niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche and the niche succession time, the methylation/demethylation process, and the randomness due to sampling. As a consequence, methylation pattern studies can reveal niche characteristics but also require appropriate statistical methods. The analysis of methylation patterns sampled from colon crypts is a prototype of such a study. Previous analyses were based on forward simulation of the cell content of the whole crypt and subsequent comparisons between simulated and experimental data using a few statistics as a proxy to summarize the data. In this paper we develop a more powerful method to analyze these data based on coalescent modelling and Bayesian inference. Results support a scenario where the colon crypt is maintained by a high number of stem cells; the posterior indicates a number greater than eight and the posterior mode is between 15 and 20. The results also provide further evidence for synergistic effects in the methylation/demethylation process that could for the first time be quantitatively assessed through their long-term consequences such as the coexistence of hypermethylated and hypomethylated patterns in the same colon crypt. Public Library of Science 2007-03 2007-03-02 /pmc/articles/PMC1808490/ /pubmed/17335343 http://dx.doi.org/10.1371/journal.pcbi.0030028 Text en © 2007 Nicolas et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nicolas, Pierre Kim, Kyoung-Mee Shibata, Darryl Tavaré, Simon The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title | The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title_full | The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title_fullStr | The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title_full_unstemmed | The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title_short | The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns |
title_sort | stem cell population of the human colon crypt: analysis via methylation patterns |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808490/ https://www.ncbi.nlm.nih.gov/pubmed/17335343 http://dx.doi.org/10.1371/journal.pcbi.0030028 |
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