Volume 140, Issue 4, Pages 1139-1143 (April 2011) Ancestries Hidden in Plain Sight: Methylation Patterns for Clonal Analysis  Eric R. Fearon  Gastroenterology  Volume 140, Issue 4, Pages 1139-1143 (April 2011) DOI: 10.1053/j.gastro.2011.02.027 Copyright © 2011 AGA Institute Terms and Conditions

Figure 1 Monitoring stem cell kinetics with methylation patterns—potential issues. (A) schematic representation of the intestinal architecture: Normal crypts are continuously repopulated from stem cells localized at the crypt base. Differentiated cells migrate up the crypt and eventually shed off into the lumen. New crypts can be generated by a bifurcation process termed crypt fission. (B) Propagation of CGI methylation patterns in expressed and nonexpressed genes. Methylation patterns are propagated during mitosis and there is a small chance in each cell division that a particular CpG will be de novo methylated or demethylated. At baseline, many CGIs are not methylated. Methylation patterns of CGIs overlapping regulatory elements of expressed genes might alter gene expression. These methylation patterns, therefore, can be subject to selective pressure to either acquire or lose methylated CpGs (left part of panel). In contrast, methylation of not expressed genes increases in a stochastic way during aging and represents a mitotic memory. Shared methylation patterns might be indicative of common ancestry of cell populations. Open circles = unmethylated CpGs; filled circles = methylated CpGs. (C, D) Anticipated results if methylation patterns are stably propagated (C) or not (D): CCO mutant stem cell in some crypts will repopulate the whole crypt. If methylation patterns are stably propagated over long periods of time, the clonal CCO mutant crypts should show a homogeneous methylation pattern (C). If methylation patterns are not stably propagated, clonal CCO mutant crypts are expected to show heterogeneous methylation patterns. Gastroenterology 2011 140, 1139-1143DOI: (10.1053/j.gastro.2011.02.027) Copyright © 2011 AGA Institute Terms and Conditions