We next used epigenome similarity to study the relationship between tissues and cell types, based on the similarity of diverse histone modification marks evaluated in their relevant chromatin states. Hierarchical clustering of our 111 reference epigenomes using H3K4me1 signal in Enh (Fig. 6a) showed consistent grouping of biologically-similar cell and tissue types, including ESCs, iPSCs, T-cells, B-cells, adult brain, fetal brain, digestive, smooth muscle, and heart. We also found several initially surprising but biologically-meaningful groupings: fetal brain and germinal matrix samples clustered with neural stem cells rather than adult brain, consistent with fetal neural stem cell proliferation; many ES-derived cells clustered with ESCs and iPS cells rather than the corresponding tissues, suggesting that those are still closer to pluripotent states than corresponding somatic states; adult and fetal thymus samples clustered with T-cells rather than other tissues, consistent with roles in T-cell maturation and immunity. Several marks successfully recovered these biological groupings when evaluated in their relevant chromatin states (Fig. S8), including H3K4me1 in TssA, H3K27me3 in ReprPC state, and H3K27ac in Enh states, suggesting that the signal of each mark
