By differentiation of both H1 and FF-iPSC 19.11 cells into trophoblast lineage cells with BMP4, we were able to determine the frequency at which CG-DMRs in iPSCs were transmitted through differentiation. We identified 140 hypomethylated (Fig. 4c) and 70 hypermethylated (Fig. 4d) CG-DMRs present in both FF-iPSC 19.11 cells and FF-iPSC 19.11-BMP4 trophoblasts with respect to H1 and H9 ES cells, and H1-BMP4 trophoblasts. A high proportion of the CG-DMRs in FF-iPSC 19.11 cells relative to both ES cell lines were transmitted through the differentiation process, with 88% and 46% of hypermethylated and hypomethylated CG-DMRs, respectively, still present in FF-iPSC 19.11-BMP4 trophoblasts but not in H1-BMP4 trophoblasts (Fig. 4e). These transmitted CG-DMRs were comprised of both somatic memory (Fig. 4e and Supplementary Fig. 12) and iDMR (Fig. 4e and Supplementary Fig. 13) classes. Notably, 9 of 11 hypermethylated and 57 of 119 hypomethylated CG-DMRs present in all iPSC lines were transmitted to the FF-iPSC 19.11-BMP4 trophoblast cells.
