Figure 2

Methylation tags. A) The bisulfite converted sequence of the BGN methylation tag, which contains 9 CpG sites (underlined). A capital "T" represents bisulfite conversion of a non-CpG site "C". B) Intracrypt and intercrypt distances between methylation tags. Average distances (line) change with aging according to our model of human crypt niches [11]. 95% simulation intervals (dotted lines) reflect that drift and therefore distances are stochastic and not deterministic. The lower simulation bound for intracrypt distances is zero. Intracrypt distances remain relatively constant through life because stem cell niche turnover results in the periodic loss of all stem cell lineages except one. These "bottlenecks" ensure that all cells within a crypt are relatively closely related to each other. In contrast, intercrypt distances increase with age, reflecting that methylation tags randomly drift apart in unrelated crypts. C) Examples of BGN methylation tags (5' to 3') in adjacent and branched crypts. Filled circles are methylated CpG sites and tags from individual crypts are grouped. Intracrypt and intercrypt distances are labeled.