The stem cell population of the human colon crypt: analysis via methylation patterns

PLoS Comput Biol. 2007 Mar 2;3(3):e28. doi: 10.1371/journal.pcbi.0030028. Epub 2007 Jan 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Count / methods*
  • Colon / cytology*
  • CpG Islands / genetics
  • DNA Methylation*
  • DNA Mutational Analysis / methods
  • Evolution, Molecular
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide / genetics*
  • Sequence Analysis, DNA / methods*
  • Stem Cells / cytology*
  • Stem Cells / physiology*