An omics insight into the expression of the ion transport toolkit in human cerebrovascular endothelial cells The Blood-Brain Barrier (BBB) is crucial in neurovascular coupling and for maintaining a controlled environment within the brain InterStitial Fluid (ISF) for reliable neuronal signaling. Key to these processes are intracellular calcium dynamics taking place at the level of brain endothelial cells, which influences BBB integrity by modulating tight junctions and nitric oxide production for vasodilation. However, despite its widely recognized functional role, the molecular actors that enable proper BBB functioning are often overlooked. To identify the main Ion Channels and Transporters (ICTs) contributing to the physiological role of the BBB, we carried out a transcriptional meta-analysis aggregating gene expression data from nine independent and publicly available RNA-Seq studies on the hCMEC/D3 cell line, the most widely used in vitro model of BBB. We selected 551 genes coding for ion channels, transporters, membrane ATPases, and some GPCRs. Then, using a tailor-made bioinformatics pipeline, we highlighted a signature expression profile with a potential functional and pathological significance. We identified distinct families of functionally related ICTs underpinning the most distinctive features of the human cerebrovascular endothelium, including the secretion of ISF, the maintenance of BBB integrity, the adaptive regulation of the cerebral blood flow, the uptake and extrusion of trace metals, as well as the membrane components of the endothelial calcium toolkit.

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Large-scale comparison of Ion Channel and Transporter (ICT) expression in healthy endothelium