Fig. 4: Chromatin accessibility defects lead to the abnormal transition from pluripotency to meiosis in fetal PGCs exposed to IUHG.

a PCA analysis of the developmental trajectory of fetal PGCs based on ATAC-seq data. b, c Boxplots of promoter signal accessibility for pluripotency (b) and meiosis-related (c) DEGs in IUHG conditions compared to control groups. d Venn diagrams demonstrate the overlap of pluripotency and meiosis genes (at E13.5 F), which have synergistic changes of RNA-seq and nearby ATAC-seq chromatin changes. e Genome browser track view showing the ATAC signal enrichment at core pluripotency TF binding sites around the Enpp3, Nanog, Sall4, and Tfap2c loci in female PGCs at E12.5, E13.5, and E16.5 in control and IUHG. The heatmap shows the expression of those genes. f Genome browser view showing the ATAC-seq signal enrichment at core meiosis TF binding sites around the Dmrtc2, Mael, Slc25a31, Stra8, Sycp1, and Sycp3 loci in female PGCs at E12.5, E13.5, and E16.5 in control and IUHG. The heatmap shows the expression of those genes. g–j Prediction of TF and regulatory networks that regulate pluripotency (g, h) and meiosis-associated (i, j) genes. The horizontal axis represents the difference in the number of genes of interest regulated by TFs under control and IUHG conditions, and the vertical axis represents the enrichment of TF motifs in DAR near the genes of interest. k Genome browser view showing the dynamic chromatin accessibility changes at TF binding sites around the E2f8, Klf12, Patz1, Tfdp1, and Tclf5 loci in female PGCs at E12.5, E13.5, and E16.5 in control and IUHG. The heatmap shows the expression of those genes.