title: Expression and splicing of ABC and SLC transporters in the human blood-brain barrier measured with RNAseq.
abstract: The blood-brain barrier (BBB) expresses numerous membrane transporters that supply needed nutrients to the central nervous system (CNS), consisting mostly of solute carriers (SLC transporters), or remove unwanted substrates via extrusion pumps through the action of ATP binding cassette (ABC) transporters. Previous work has identified many BBB transporters using hybridization arrays or qRT-PCR, using targeted probes. Here we have performed next-generation sequencing of the transcriptome (RNAseq) extracted from cerebral cortex tissues and brain microvessel endothelial cells (BMEC) obtained from two donors. The same RNA samples had previously been measured for transporter expression using qRT-PCR (Geier et al., 2013), yielding similar expression levels for overlapping mRNAs (R=0.66, p<0.001). RNAseq confirms a number of transporters highly enriched in BMECs (e.g., ABCB1, ABCG2, SLCO2B1, and SLC47A1), but also detects novel BMEC transporters. Multiple splice isoforms detected by RNAseq are either robustly enriched or depleted in BMECs, indicating differential RNA processing in the BBB. The Complete RNAseq data are publically available (GSE94064).
authors.affiliation: College of Medicine, Center for Pharmacogenomics, Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Suhy
authors.affiliation: Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Webb
authors.affiliation: College of Medicine, Center for Pharmacogenomics, Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Papp
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Ethan G
authors.initials: EG
authors.lastname: Geier
authors.affiliation: College of Medicine, Center for Pharmacogenomics, Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA. Electronic address: wolfgang.sadee@osumc.edu.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sadee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D017398:Alternative Splicing; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000070590:Solute Carrier Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000070590:Solute Carrier Proteins
keywords: Blood brain barrier; Expression; Human; RNAseq; SLC and ABC transporters; Splicing