Suhy Adam M, Webb Amy, Papp Audrey C, Geier Ethan G, Sadee Wolfgang
College of Medicine, Center for Pharmacogenomics, Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
Eur J Pharm Sci. 2017 May 30;103:47-51. doi: 10.1016/j.ejps.2017.02.010. Epub 2017 Feb 7.
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).
血脑屏障（BBB）表达众多膜转运蛋白，这些转运蛋白为中枢神经系统（CNS）提供所需营养物质，主要由溶质载体（SLC转运蛋白）组成，或通过ATP结合盒（ABC）转运蛋白的作用，经由外排泵清除不需要的底物。先前的研究工作已使用杂交阵列或qRT-PCR，并采用靶向探针鉴定了许多血脑屏障转运蛋白。在此，我们对从两名供体获取的大脑皮质组织和脑微血管内皮细胞（BMEC）中提取的转录组进行了二代测序（RNAseq）。相同的RNA样本先前已使用qRT-PCR检测过转运蛋白表达（Geier等人，2013年），重叠mRNA的表达水平相似（R = 0.66，p < 0.001）。RNAseq证实了一些在BMEC中高度富集的转运蛋白（例如ABCB1、ABCG2、SLCO2B1和SLC47A1），但也检测到了新的BMEC转运蛋白。RNAseq检测到的多种剪接异构体在BMEC中要么大量富集，要么缺失，表明血脑屏障中存在不同的RNA加工过程。完整的RNAseq数据已公开可用（GSE94064）。
