Extended Data Fig. 1: Gene regulatory networks dynamically remodel during human cardiomyocyte differentiation.

a, Flow cytometry analysis shows the percentage of cell types generated at each cardiac developmental stage as assessed by the indicated markers. b, Heatmap shows cell-type cardiac enhancers through comparison with ENCODE-derived cell line enhancer data. c, CREs are enriched in intergenic and intronic regions during cardiomyocyte differentiation. d, Number of CREs for different epigenomic assays are shown across the six stages of human vCM differentiation. e, Bar plot shows the number of CREs that are gained or lost compared to the preceding stage during human ventricular cardiomyocyte differentiation. f, Analyzing the ratio of active enhancers (H3K27ac⁺/H3K4me1⁺) to all enhancers (H3K4me1⁺) reveals increased enhancer utilization during human vCM differentiation. g, Heatmap displays enhancer activity as assessed by H3K27ac signal during in vitro vCM differentiation and in purified human fetal CMs. PSC, human pluripotent stem cells; Mes, mesoderm; CMes, cardiac mesoderm; CP, cardiac progenitor; CM, cardiomyocyte; vCM, ventricular cardiomyocyte; fvCM, fetal ventricular cardiomyocyte; CRE, cis-regulatory region; pos., positive; snRNA, small nuclear RNA; snoRNA, small nucleolar RNA; UTR, untranslated region; pseudo, pseudogene; TTS, transcription termination site; ncRNA; non-coding RNA; miRNA, microRNA; HUVEC, human umbilical vein endothelial cells; NHEK, normal human epidermal keratinocytes; fvCM, fetal ventricular cardiomyocyte.