Timing of loss of imprinting in human embryonic lineages. (A) Schematic representation of the developmental origins of the extraembryonic cell types is shown, with TE-derived cells (dark blue), ICM-derived cells (green), and cells with mixed origin (turquoise) denoted. (B) The distribution of DNA methylation for known placental-specific DMRs that lose DNA methylation in somatic tissues (N = 14) is shown for extraembryonic cell types isolated from term placenta. Methylation for trophoblast and mesenchyme is an average from 1st, 2nd, and 3rd trimester samples. TE-derived cells (dark blue), ICM-derived cells (green), and cells with mixed origin (turquoise) are denoted. Extraembryonic cell types are ordered based on the approximate timing in development when each cell type is derived. The window of epigenetic reprogramming highlights the period in which DNA methylation at placental-specific DMRs is likely being erased in the ICM-derived lineage.