title: Analysis of the brain mural cell transcriptome.
abstract: Pericytes, the mural cells of blood microvessels, regulate microvascular development and function and have been implicated in many brain diseases. However, due to a paucity of defining markers, pericyte identification and functional characterization remain ambiguous and data interpretation problematic. In mice carrying two transgenic reporters, Pdgfrb-eGFP and NG2-DsRed, we found that double-positive cells were vascular mural cells, while the single reporters marked additional, but non-overlapping, neuroglial cells. Double-positive cells were isolated by fluorescence-activated cell sorting (FACS) and analyzed by RNA sequencing. To reveal defining patterns of mural cell transcripts, we compared the RNA sequencing data with data from four previously published studies. The meta-analysis provided a conservative catalogue of 260 brain mural cell-enriched gene transcripts. We validated pericyte-specific expression of two novel markers, vitronectin (Vtn) and interferon-induced transmembrane protein 1 (Ifitm1), using fluorescent in situ hybridization and immunohistochemistry. We further analyzed signaling pathways and interaction networks of the pericyte-enriched genes in silico. This work provides novel insight into the molecular composition of brain mural cells. The reported gene catalogue facilitates identification of brain pericytes by providing numerous new candidate marker genes and is a rich source for new hypotheses for future studies of brain mural cell physiology and pathophysiology.
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.|Integrated Cardio Metabolic Centre (ICMC), Karolinska Institute, Novum, SE-141 57 Huddinge, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Vanlandewijck
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.|Integrated Cardio Metabolic Centre (ICMC), Karolinska Institute, Novum, SE-141 57 Huddinge, Stockholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Raschperger
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Maarja
authors.initials: M
authors.lastname: Andaloussi Mäe
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Bongnam
authors.initials: B
authors.lastname: Jung
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lebouvier
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hofmann
authors.affiliation: Division of Neurosurgery, Zürich University Hospital, Zürich University, Zürich, Switzerland.
authors.forename: Annika
authors.initials: A
authors.lastname: Keller
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.|Integrated Cardio Metabolic Centre (ICMC), Karolinska Institute, Novum, SE-141 57 Huddinge, Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D051379:Mice; D055806:Microvessels / Q000166:cytology*; D020286:Pericytes / Q000502:physiology*; D017423:Sequence Analysis, RNA; D013194:Staining and Labeling