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. Author manuscript; available in PMC: 2021 Jul 9.
Published in final edited form as: Cell Rep. 2021 Jun 8;35(10):109215. doi: 10.1016/j.celrep.2021.109215

Figure 4. Global hypomethylation and emergent naive pluripotency markers in terminal XIE.

Figure 4.

(A) Autosomal methylation distributions across female hPSC clusters (A–F, red shades) and their KS distances relative to male hPSC distribution (teal).

(B) Chromosome-resolved DMPs of the final XIE transitions (4 or 5). Total number of probes changing for autosomes and X listed with colors corresponding to increasing (red) or decreasing (blue) DNAme. The transparency is on a continuous scale based on the β-differential.

(C) As in (B), but plotting differentially expressed genes (DESeq2) with concordant DNAme changes (B) and/or ATAC changes. The transparency is on a continuous scale reflecting the log2FC.

(D) Transition- and autosome/X-resolved differentially expressed genes annotated in the COSMIC cancer gene census (Sondka et al., 2018) (also listed in Table S4).

(E) Median X:autosome ratio for each female sample cluster (Wilcoxon p value relative to cluster A).

(F) Differential expression scatterplot of transition-4/−5-specific genes (y axis) over log2FCs (x axis) of these genes between naive and primed hPSCs from Kilens et al. (2018).

(G) Comparison of expression changes in transition-4/−5-specific differential genes (dark red) relative to corresponding changes (gray) in naive versus primed hPSCs from Kilens et al. (2018).

(H) Cumulative changes (relative to cluster A) in all differentially expressed HERVs identified by Telescope (Bendall et al., 2019) (VST + batch-corrected/log2-transformed). Only significantly overrepresented HERVs (hypergeometric p ≤ 0.1) are labeled by colors (others in gray). Color legend lists total counts of differentially expressed HERV classes (with hypergeometric significance indicated as *p < 0.1, **p < 0.05, ***p < 0.01, ****p < 0.001).

(I) Tally of differentially expressed HERV classes (H) overlapped by significantly differential ATAC peaks (Fisher right-side p value indicated as *p < 0.01, **p < 0.001, ***p < 0.0001). Negative overlaps indicate overlaps by closing ATAC peaks, and positive by opening peaks.