Fig. 4

Gene co-regulation of TFs, miRNAs and lncRNAs on the early and late stages of in vivo CM development. A Enrichment analysis of the co-regulated genes of TF-miRNA and TF-lncRNA related to heart development, function and disease during in vivo fetal embryo-derived atrial and ventricular CM development. The p values represent significance of the enrichment analysis based on hypergeometric distribution. B and C Comparison of the differentially expressed heart genes regulated by the cardiac TFs, miRNAs or lncRNAs. The datasets of hPSC-CMs and fetal embryo-derived atrial and ventricular CMs at the early stages (B) and late stages (C) were used. The number in the Venn diagram shows the number of heart targets shared by the different datasets. The numbers of “conserved heart targets” shown in the parentheses indicate how many target genes are regulated by at least one common TF, miRNA or lncRNA between hPSC-CMs and embryo-derived CMs, i.e., CM-AE, CM-AL, CM-VE and CM-VL. The associated pathways, processes and heart diseases with the conserved and specific target gene programs are shown correspondingly. The black bars correspond to conserved targets, and the open bars are those that are specific to either CM-AE, CM-AL, CM-VE and CM-VL (i.e., not conserved relative to hPSC-CMs). D and E The percentage of the conserved targets of miRNA-TF (D) and lncRNA-TFs (E) in total heart genes of hESC-CMs at the early and late stages