Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes.
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 pericyte-deficient brain microvessels isolated from platelet-derived growth factor (PDGF-B)-/- and PDGF beta receptor (PDGFRbeta)-/- mouse mutants. The approach was validated by the identification of known pericyte markers among the most down-regulated genes in PDGF-B-/- and PDGFRbeta-/- microvessels. Of candidates for novel pericyte markers, we selected ATP-sensitive potassium-channel 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
Cecilia
C
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm, Sweden.
He
Liqun
L
Takemoto
Minoru
M
Norlin
Jenny
J
Asker
Noomi
N
Hellström
Mats
M
Lindahl
Per
P
Betsholtz
Christer
C
D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000098:blood supply / Q000166:cytology*; D002135:Calcium-Binding Proteins; D002196:Capillaries / Q000166:cytology*; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D046228:Microarray Analysis / Q000379:methods*; D020286:Pericytes / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis / Q000172:deficiency*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000172:deficiency*; D011955:Receptors, Drug; D012097:Repressor Proteins / Q000032:analysis; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying; D020574:Proto-Oncogene Proteins c-sis; D011955:Receptors, Drug; D012097:Repressor Proteins; D064233:Sulfonylurea Receptors; C092520:uK-ATP-1 potassium channel; D020797:Receptor, Platelet-Derived Growth Factor beta