Chromatin compartment transitions in lamin A/C haploinsufficient hiPSC-CMs. (A) Heatmap of all significantly different A/B compartment scores (Hi-C matrix PC1; P < 0.05 by one-way ANOVA; n = 2 differentiations; Table S5) in 500-kb bins that changed PC1 sign between two or more conditions. Positive and negative PC1 indicate A and B compartmentalization, respectively. (B) Representative log-transformed contact probability maps for chromosome 19. TADs are visible as squares along the diagonal. TADs within the same compartment interact off the diagonal as indicated by the symmetrical checkerboard patterns. Two genomic regions that show different compartmentalization in mutant hiPSC-CMs are indicated by dashed boxes to highlight the differences in contact probabilities with other genomic regions off the diagonal. (C) Linear dimensionality reduction by principal component (PC) analysis of A/B compartment scores from Hi-C data of mutant and corrected hiPSC-CMs, and hESC-CMs sampled at different time points of differentiation. (D) Significance of the overlap between changes in A/B compartments in mutant hiPSC-CMs and those occurring during hESC-CM differentiation. The number of genomic bins within each of the categories is indicated, and P values were calculated by χ² tests. (E) Representative genomic tracks of chromatin compartmentalization for chromosome 19 and a section of chromosome 5. Positive and negative Hi-C matrix PC1 scores are shown in red and blue, and indicate 500-kb genomic bins in the A and B compartments, respectively. Genomic regions that transition from A to B during hESC-CM differentiation but remain in A in mutant hiPSC-CMs (noted as B to A) are indicated by dashed boxes. Selected genes found within such regions are listed (refer to Fig. 8 and Fig. S5).