Fig. 3

Programmed DNA methylation heterogeneity in human pre-implantation embryos. a, b Box plots of the observed DNA methylation heterogeneity of promoters in the 4-cell stage (a) and 8-cell stage (b) during human embryogenesis. Promoters were classified into 5 classes based on their DNA methylation states in the zygote stage. For each box, the point indicates the average DNA methylation heterogeneity of the class. Student’s t test was performed for comparisons between adjacent classes (***p value < 0.001; **p value < 0.01; *p value < 0.05; ^-p value > 0.05). The embryo with the largest number of high-quality scBS-seq data (more than 20% of all CpG sites detected) at each stage were used to calculate the DNA methylation heterogeneity. c Estimated parameters of the first three cell cycles during human embryogenesis. The lines link the mean values of the parameters in each cell cycle. The gray shaded areas represent the 95% confidence intervals around the mean values. d, e Box plots of the predicted DNA methylation heterogeneity of promoters in the 4-cell stage (d) and 8-cell stage (e) during human embryogenesis. Promoters were classified into 5 classes based on their DNA methylation states in the zygote stage. For each box, the point indicates the average DNA methylation heterogeneity of the class. Student’s t test was performed for comparisons between adjacent classes (***p value < 0.001). f 3D plots of predicted DNA methylation heterogeneity scores at the 8-cell stage for simulated values of p and d for five classes of promoters. Here, the parameter u is a constant (u = 0.03). The colors represent the predicted heterogeneity scores