Finally, we validated the cardiac disease modeling potential in Isl1-Cre, RFP+, Cxcr4+/− CPC populations by knocking down Tbx5 and Tbx1. Importantly, Tbx5 knockdown only affected cardiogenesis in Cxcr4− CPCs (Supplementary Fig. 5e), whereas Tbx1 knockdown only had an effect on Cxcr4+ CPCs (Supplementary Fig. 5f), similar to the knockdown experiments in Hcn4−GFP+ and Tbx1-Cre, RFP+ CPCs (Supplementary Fig. 2h, i). This evidence concerns the gene ISL1 and heart disorder.