Studies using primary VICs from multiple species and endothelial cells differentiated from the human induced pluripotent stem cells (hiPSCs) of patients with the NOTCH1 mutations have begun to uncover the deep molecular mechanisms underlying the CAVD progression associated with the NOTCH1 haploinsufficiency in humans (Figure 4). This evidence concerns the gene NOTCH1 and congenital bilateral aplasia of vas deferens from CFTR mutation.