P450 oxidoreductase (POR) Regulates Barrier Maturation by Mediating Retinoic Acid Metabolism in a Model of the Human BBB

The blood-brain barrier (BBB) is a multicellular neurovascular unit (NVU) that allows the selective passage of necessary molecules into the central nervous system (CNS), while limiting the entry of neurotoxins and most drugs. A crosstalk with pericytes and neural cells mediates the acquisition of specialized properties, such as the formation of tight junctions (TJs), in brain microvascular endothelial cells (BMECs). TJs limit the paracellular passage of solutes, thereby regulating CNS homeostasis. However, the mechanisms by which NVU cells communicate to mediate TJ formation remains a mystery. Retinoic acid (RA), a key signaling molecule during vertebrate embryonic development, is commonly used to enhance functional barrier properties in in vitro BBB models. However, its physiological relevance and affected pathways are not fully understood. induced pluripotent stem (iPS)-derived brain microvascular endothelial-like cells, from healthy controls, POR-deficient patients and POR mutated lines . Each line was differentiated with 0, 0.25, 1, 10 uM of all-trans retinoic acd (RA), in triplicates . These triplicates include 2 technical duplicates and an one additional biological replicate.