Dissecting gene expression at the blood-brain barrier

Abstract

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published data sets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier data sets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published data sets, combined with forthcoming genomic and proteomic blood-brain barrier data sets, will continue to fuel the molecular genetic revolution of.

Keywords: blood-brain barrier; brain endothelial cells; expression profiling; genomics; transcriptome.

Figure 1

Techniques for isolating BECs. (A) Laser capture microdissection or (B) mechanical filtration of brain microvessels can be used to isolate segments of the neurovascular unit (C). FACS or other antibody based purification (D) can be performed to isolate BECs acutely. Isolated microvessels (B) and purified BECs (D) can be further cultured in a trans-well system (E) or other relevant in vitro culture systems (F). Experiments based on the neurovascular unit (C), purified primary BECs (D) and cultured BECs (E,F) will each provide valuable, but different insights into the biology of the BBB.