Fig. 1: Epigenetic variation increases as cells are differentiated, direct relationship to genetic variation becomes weaker.

A Study Design Graphic. Renal epithelial cells collected from the fresh urine samples of two related donors (F1 and M1) and one unrelated donor (F2) were reprogrammed into iPSCs.: lines F1_1, F1_2, F1_3, M1_1, M1_2, and F2_1. Each line has a technical replicate that was grown simultaneously. Each iPSC line, as well as NSCs, motor neurons, and monocytes differentiated from respective iPSC lines, were assayed for WGBS, ATAC-seq, and RNA-seq to measure DNA methylation, chromatin accessibility, and gene expression. B PCA plots of CpG methylation. Each point is a line colored by cell type, and each technical replicate has the same shape. Observations are the methylation levels (percentages) of CpGs with variance > 0.05 among samples. C PCA plots of ATAC reads within peaks. Each point is a line colored by cell type, and each technical replicate has the same shape. PCAs of reads within ATAC peaks for each of the differentiated cell lines. Each observation is the number of reads under a peak, normalized by library size in DiffBind. D PCA plots of exonic RNA-seq reads. Each point is a line colored by cell type, and each technical replicate has the same shape. Each observation is the number of exonic reads within a gene, normalized by sequencing depth and RNA composition in DESeq2. E Bar plots of the number of differentially methylated CpGs between each pair of lines in each of the differentiated cell lines. Bars are colored by the relationship between the donors of lines (same donor (orange), related donors (green), unrelated donors (purple)). F Bar plots of the number of differentially expressed genes between each pair of lines in each of the differentiated cell lines. Bars are colored by the relationship between the donors of lines. Color coding is the same as in (E). G Bar plots of the number of differentially accessible ATAC peaks between each pair of lines in each of the differentiated cell lines. Color coding is the same as in (E). Source data are provided as a Source Data file.