Fig. 4: Functional analysis of ERRg using iPSCMs.
a, Volcano plot analysis. Each point represents a ChIP-seq experiment and is highlighted as red for cardiovascular cells, green for induced pluripotent stem cell-derived cardiac cells, blue for muscle cells and gray for other cell types. P values were calculated with two-tailed Fisher’s exact probability test. The x axis shows log2-transformed fold enrichment of transcription factor in 150 AF-associated loci, compared to 150 randomly selected genomic regions. The y-axis shows log10-transformed P value for enrichment. The dashed line indicates the significance threshold level of P = 0.05, and the dotted line indicates P = 0.05/15,109. b, Comparison of gene expression changes in iPSCMs with and without GSK5192 (an inverse agonist of ERRg) administration (n = 25 and n = 23, respectively). Ion channels and sarcomere genes were selected from the downstream genes of ERRg based on the binding profiles of ChIP-seq data using target genes function in ChIP-Atlas. c,d, Motion analysis of iPSCMs using the SI8000 Cell Motion Imaging System. The y axis represents the magnitude of cellular motion over time. GSK5182-treated iPSCMs show a decrease in spontaneous beating rate and irregularity (c). Beating rate and contraction duration analyzed using the SI8000 Cell Motion Imaging System (n = 10) (d). e–g, Calcium handling analysis of iPSCMs. Calcium transient signal was recorded before and after isoproterenol administration (e). We measured averaged peak counts (beating rates) and peak with duration at 80% repolarization (PWD80) (n = 6) (f). The increases in beating rate were compared before and after isoproterenol administration (n = 6) (g). In b, d, f and g, data are presented as mean ± s.e.m., and P values from a two-sided Student’s t test are shown.
