“…hPSCs are an attractive model system to complement in vivo animal studies because they (i) are human, (ii) permit investigation of developmental processes in contrast to primary or immortalized cells, (iii) are highly scalable, (iv) can be derived from patients to facilitate disease modeling and autologous coculture systems, and (v) are genetically tractable. While widely used hPSC-based BBB models are useful for measuring molecular permeabilities and have been employed to understand genetic contributions to barrier dysfunction (Vatine et al, 2016(Vatine et al, , 2019Lim et al, 2017), they have not been shown to proceed through a definitive endothelial progenitor intermediate (Lippmann et al, 2012;Lu et al, 2021) and express epithelial-associated genes (Qian et al, 2017;Delsing et al, 2018;Vatine et al, 2019;Lu et al, 2021). Thus, new models with developmentally relevant differentiation trajectories and definitive endothelial phenotype are needed for improved understanding of developmental mechanisms.…”