The PluripotentLowVar/SomaticHighVar category contained several clusters of CpG sites that were hypermethylated in all of the hPSCs and the majority of somatic samples, but unmethylated in a small number of somatic samples containing related cell types (Figure 1C). The genes associated with each cluster of CpGs were enriched for functional categories related to the known functions of the corresponding samples (Figure S1C–G). For example, CpG sites that were uniquely hypomethylated in the blood, spleen, and lymph node samples were enriched for the immune system process, immune response, and defense response categories (Figure S1G). Since these genes were uniformly hypermethylated in the pluripotent state and in unrelated somatic cell types, it appeared that cell type-specific genes underwent selective DNA demethylation during differentiation, and led us to explore this phenomenon at higher resolution.
