Our results obtained from the PP2 and EPs stages showed that FOXA2 haploinsufficiency led to a significant reduction in the expression of the monogenic diabetes-associated genes, such as PDX1, HNF4A, HNF1A, NEUROD1, NGN3, PAX4, ABCC8, KCNJ11, GATA6, and MNX1. In addition, several key pancreatic development-specific TFs were significantly downregulated in PP2 and EPs derived from FOXA2+/− iPSCs, such as NKX6.1, NKX6.2, SOX9, NKX2.2, ISL1, and GATA6, among others. Here, ISL1 is linked to diabetes mellitus.