Fig. 1

Differential 3D genome landscape profile of ESCs versus EPSCs. A Schematic illustration of the in vitro models used for studying the 3D genome of distinct pluripotent states, expanded pluripotent stem cells (EPSC), and naïve embryonic stem cells (ESC). TE-centric genome analysis was performed by 2 strategies. Firstly by combined analysis of genome-wide Hi-C with enhancer-mark H3 K27ac ChIP-seq, and secondly by enhancer-centric H3 K27ac HiChIP. The genome looping surrounding TE and accessible regions defined by ATAC-seq were considered. B Differential compartments identified from pairwise comparison between ESC and EPSC. The colors represent six different types of compartment transitions. Within compartment A, we distinguish between high-strength to low-strength (dark red, n = 108) and low-strength to high-strength (light red, n = 110) transitions. There are 44 transitions from compartment A-to-B, and 923 transitions from compartment B-to-A. Within compartment B, we distinguish between high-strength to low-strength (light green, n = 26) and low-strength to high-strength (dark green, n = 87). C Expression fold change of genes undergoing compartment switch. D Number of differential boundaries identified through pairwise comparisons by TADCompare package. The differential boundaries were classified into 5 categories. E Scatterplot of EPSC up- (red dots) and downregulated (blue dots) genes located within differential TAD. Several examples of EPSC upregulated genes were labelled out. The number of upregulated genes located within each category of differential TAD was shown in the bar chart. F Hi-C heatmap showing TAD reorganization around Tfap2a gene locus. G Pile-up analyses of significantly identified chromatin loops using Hi-C data of ESC and EPSC. Number of chromatin loops for each potency state was labelled. H Number of differentially expressed genes enriched in the anchors of specific or consistent chromatin loops. I H3 K27ac binding signal and Hi-C interactions around EPSC-specific gene H19. J Boxplot showing the decrease of contacts at the ESC-loops in EPSC. The signal was quantified using H3 K27ac HiChIP. K H3 K27ac binding signal and HiChIP interactions around EPSC-downregulated gene Axin2