FIGURE 9.

By using bone morphogenetic protein (BMP) receptor mutant congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) patient induced pluripotent stem cells (iPSCs) together with single-cell RNA sequencing (scRNA-seq) on inhibitors of DNA-binding proteins (IDs) knockout (KO) human embryonic stem cells (hESCs), we found that BMPR2 signals via IDs and USP9X to drive cardiac differentiation. In normal controls, BMPR2 signals via ID1, leading to the inhibition of E47 binding on the USP9X promoter, which regulates USP9X gene expression during cardiomyocyte differentiation. In CHD-PAH patients with BMP receptor mutations, the loss of ID1 and ID3 expression contributes to CM dysfunction.