Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate
Tyler M. Lu, Sean Houghton, Tarig Magdeldin, José Gabriel Barcia Durán, Andrew P. Minotti, Amanda M. Snead, Andrew A. Sproul, Duc-Huy T. Nguyen, Jenny Xiang, Howard A. Fine, Zev Rosenwaks, Lorenz Studer, Shahin Rafii, Dritan Agalliu, David Redmond, Raphaël Lis
Abstract
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.