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      The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial Cells

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          Abstract

          The blood-brain barrier (BBB) maintains brain homeostasis and limits the entry of toxins and pathogens into the brain. Despite its importance, little is known about the molecular mechanisms regulating the development and function of this crucial barrier. In this study we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are enriched in the BBB forming endothelial cells of the brain. Through this comparison we have identified novel tight junction proteins, transporters, metabolic enzymes, signaling components, and unknown transcripts whose expression is enriched in central nervous system (CNS) endothelial cells. This analysis has identified that RXRalpha signaling cascade is specifically enriched at the BBB, implicating this pathway in regulating this vital barrier. This dataset provides a resource for understanding CNS endothelial cells and their interaction with neural and hematogenous cells.

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          Most cited references39

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          Pericyte loss and microaneurysm formation in PDGF-B-deficient mice.

          Platelet-derived growth factor (PDGF)-B-deficient mouse embryos were found to lack microvascular pericytes, which normally form part of the capillary wall, and they developed numerous capillary microaneurysms that ruptured at late gestation. Endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells. Pericytes may contribute to the mechanical stability of the capillary wall. Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts.
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            Phenotypic heterogeneity of the endothelium: II. Representative vascular beds.

            Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system.
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              Blood-brain barrier delivery.

              Neuropharmaceutics is the largest potential growth sector of the pharmaceutical industry. However, this growth is blocked by the problem of the blood-brain barrier (BBB). Essentially 100% of large-molecule drugs and >98% of small-molecule drugs do not cross the BBB. The BBB can be traversed because there are multiple endogenous transporters within this barrier. Therefore, brain drug development programs of the future need to be re-configured so that drugs are formulated to enable transport into the brain via endogenous BBB transporters.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                29 October 2010
                : 5
                : 10
                : e13741
                Affiliations
                [1 ]Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America
                [2 ]Department of Neurobiology, Stanford University School of Medicine, Stanford, California, United States of America
                [3 ]Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America
                [4 ]Department of Biomedical Informatics, Stanford University School of Medicine, Stanford, California, United States of America
                Boston University School of Medicine, United States of America
                Author notes

                Conceived and designed the experiments: RD JDC BAB. Performed the experiments: RD LZ DA JDC. Analyzed the data: RD LZ DA AK. Wrote the paper: RD BAB.

                Article
                10-PONE-RA-18004R1
                10.1371/journal.pone.0013741
                2966423
                21060791
                f37db0c3-6049-4b11-9bfe-43d3af65f4ec
                Daneman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 April 2010
                : 24 August 2010
                Page count
                Pages: 16
                Categories
                Research Article
                Cardiovascular Disorders
                Genetics and Genomics
                Neurological Disorders
                Cell Biology/Cell Adhesion
                Developmental Biology/Molecular Development
                Developmental Biology/Neurodevelopment
                Genetics and Genomics/Comparative Genomics
                Neuroscience/Neurodevelopment
                Neuroscience/Neuronal and Glial Cell Biology
                Neurological Disorders/Cerebrovascular Disease

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                Uncategorized

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