Figure 2.

(A) Methylation tags represented as binary strings (0 = unmethylated and 1 = methylated) are sampled from individual crypts. Crypts contain unmethylated tags at birth and if tags do not drift. (B) When tags drift, they may differ within and between adult crypts. Differences depend on stem cell numbers and whether they are immortal or can be lost with replacement (stem cell niche). Trees illustrate these different scenarios. If stem cells are immortal, tags will reflect lifelong divergence, and numbers of unique tags will be proportional to numbers of crypt stem cells. In contrast, stochastic bottlenecks recur with a stem cell niche, and some unique tags will be lost. Numbers of unique tags and differences between tags within a crypt will be variable and reflect the time since the last bottleneck. Quantitative comparisons of methylation tags between and within crypts can distinguish between these scenarios.