Fig. 4

Aging but not differentiation leads to increasing entropy. a-b. Example methylation profiles of epialleles (4 CpGs on chr7 at positions 38,557,438, 38,557,457, 38,557,459, and 38,557,489) that have a large change in methylation entropy with age. Each row represents data from four consecutive CpG sites in a single sequenced allele (black: methylated, gray: unmethylated). a The left shows colon stem cells (Lgr5-GFP +) in a young (4 months) mouse vs the same loci at the right in old (24 months) mouse. (b) Same as a, but colon nonstem cells (Lgr5 − GFP −). c PCA plot constructed using Jensen-Shannon distances (JSDs) for 270 epialleles detected in all samples. The PCA shows clustering by age but not by tissue of origin. d Scatterplots showing the change in Jensen-Shannon distance (JSD) on the x-axis vs change in methylation on the y-axis in the colon between (left) young and old stem cells (Lgr5 − GFP +), and (right) young and old nonstem cells (Lgr5 − GFP −). e Scatterplot of CpG sites that have a JSD > 0.2 in old (24 months) in either stem cells, nonstem cells, or both in COL, USI, and LSI