National Academy of Sciences, Proceedings of the National Academy of Sciences, 8(118), 2021
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Significance Human PSC-derived iBMECs have been generated to study disease mechanisms and drug development for neurological disorders. However, their full transcriptomic characterization is unclear, which could result in inaccurate physiological studies and development of treatments with ineffective clinical outcomes. Utilizing a comprehensive transcriptomic metaanalysis validated by physiological studies, we find that many current protocols used to generate iBMECs produce a homogenous epithelial cell population. Overexpression of ETS transcription factors reprogram these cells into phenotypic endothelial cells (rECs) which recapitulate certain vascular functions, albeit lacking expression of some organotypic transporter genes and high electrical resistance in vitro. Nevertheless, they represent a crucial step toward the generation of an in vitro model suitable for physiological and pharmaceutical studies of the blood–brain barrier.