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Microarray analysis of blood microvessels from PDGF‐B and PDGF‐Rβ mutant mice identifies novel markers for brain pericytes
Author(s) -
Bondjers Cecilia,
He Liqun,
Takemoto Minoru,
Norlin Jenny,
Asker Noomi,
Hellström Mats,
Lindahl Per,
Betsholtz Christer
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4944fje
Subject(s) - pericyte , biology , platelet derived growth factor receptor , pdgfrb , microbiology and biotechnology , microvessel , mural cell , sulfonylurea receptor , angiogenesis , growth factor , pathology , receptor , cancer research , vascular smooth muscle , endothelial stem cell , gene , genetics , endocrinology , medicine , protein subunit , smooth muscle , in vitro
Normal blood microvessels are lined by pericytes, which contribute to microvessel development and stability through mechanisms that are poorly understood. Pericyte deficiency has been implicated in the pathogenesis of microvascular abnormalities associated with diabetes and tumors. However, the unambiguous identification of pericytes is still a problem because of cellular heterogeneity and few available molecular markers. Here we describe an approach to identify pericyte markers based on transcription profiling of pericytedeficient brain microvessels isolated from platelet‐derived growth factor (PDGF‐B) –/– and PDGF beta receptor (PDGFRβ) –/– mouse mutants. The approach was validated by the identification of known pericyte markers among the most down‐regulated genes in PDGF‐B –/– and PDGFRβ –/– microvessels. Of candidates for novel pericyte markers, we selected ATP‐sensitive potassiumchannel Kir6.1 (also known as Kcnj8) and sulfonylurea receptor 2, (SUR2, also known as Abcc9), both part of the same channel complex, as well as delta homologue 1 (DLK1) for in situ hybridization, which demonstrated their specific expression in brain pericytes of mouse embryos. We also show that Kir6.1 is highly expressed in pericytes in brain but undetectable in pericytes in skin and heart. The three new brain pericyte markers are signaling molecules implicated in ion transport and intercellular signaling, potentially opening new windows on pericyte function in brain microvessels.—Bondjers, C., He, L., Takemoto, M., Norlin, J., Asker, N., Hellström, M., Lindahl, P., Betsholtz, C. Microarray analysis of blood microvessels from PDGF‐B and PDGF‐Rβ mutant mice identifies novel markers for brain pericytes. FASEB J. 20, E1005–1013 (2006)