Methylation clocks - individual colon, small intestine and endometrial crypts

We developed DNA methylation clocks where ongoing (de)methylation causes the clock to ‘tick-tock’ back-and-forth between methylated and unmethylated states. We identified tick-tock CpG sites using standard methylation arrays and developed a mathematical modelling framework to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than colon (6.5 ± 1.0 vs 5.8 ± 1.7 stem cells/crypt) with slower stem cell replacement in small intestine (0.79 ± 0.5 vs 1.1 ± 0.8 replacements/stem cell/year). Germline APC mutation increased the number of replacements per crypt (13.0 ± 2.4 replacements/crypt/year vs 6.9 ± 4.6 for healthy colon).EGA study EGAS00001005514