Endothelial progenitor cell susceptibility to DNA damaging and DDR-modulating compounds determines endothelial differentiation accuracy

• EC d4 are most vulnerable towards Dox-induced cytotoxicity independent of drug transport. • EC d4 and EC d6 display higher levels of drug-induced DSB as compared to mESC. • Dox treatment of EPC causes functional impairments in differentiated progeny, including mitochondrial dysfunction and barrier defects. • Pharmacological protection of EPC from Dox damage may reduce late cardiotoxicity in anticancer regimens.