The stem cell population of the human colon crypt:: Analysis via methylation patterns
The stem cell population of the human colon crypt:: Analysis via methylation patterns
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DOI：
10.1371/journal.pcbi.0030028
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发表时间：
2007-03-01
影响因子：
4.3
通讯作者：
Tavare, Simon
中科院分区：
文献类型：
--
作者：
Nicolas, Pierre;Kim, Kyoung-Mee;Tavare, Simon
甲基化模式的分析是一个很有前途的方法来研究细胞群体的谱系在一个有机体。在干细胞-生态位场景中，采样的甲基化模式是生态位结构特征（如生态位内干细胞数量和生态位演替时间）、甲基化/去甲基化过程以及采样随机性之间复杂相互作用的随机结果。因此，甲基化模式研究可以揭示生态位特征，但也需要适当的统计方法。从结肠隐窝取样的甲基化模式分析是此类研究的原型。先前的分析是基于对整个隐窝细胞含量的前向模拟，然后使用一些统计数据作为代理来总结数据，将模拟数据与实验数据进行比较。在本文中，我们开发了一种基于聚结模型和贝叶斯推理的更强大的方法来分析这些数据。结果支持结肠隐窝由大量干细胞维持的情况；后模表示大于8的数，后模在15到20之间。研究结果还为甲基化/去甲基化过程中的协同效应提供了进一步的证据，这一协同效应首次可以通过其长期后果（如同一结肠隐窝中高甲基化和低甲基化模式的共存）进行定量评估。
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.