Microarray analysis of blood microvessels from PDGF-RB and PDGF-Rβ mutant mice identifies novel markers for brain pericytes
Microarray analysis of blood microvessels from PDGF-RB and PDGF-Rβ mutant mice identifies novel markers for brain pericytes
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DOI：
10.1096/fj.05-4944fje
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发表时间：
2006-08-01
期刊：
影响因子：
4.8
通讯作者：
Betsholtz, Christer
中科院分区：
文献类型：
--
作者：
Bondjers, Cecilia;He, Liqun;Betsholtz, Christer
正常的微血管由周细胞排列，周细胞通过知之甚少的机制促进微血管的发育和稳定。周细胞缺乏与糖尿病和肿瘤相关的微血管异常的发病机制有关。然而，由于细胞的异质性和可用的分子标记物很少，周细胞的明确鉴定仍然是一个问题。在这里，我们描述了一种方法，以确定周细胞标记物的基础上，周细胞缺陷的脑微血管从血小板衍生生长因子（PDGF-B）-/-和PDGF β受体（PDGFR β）-/-小鼠突变体分离的转录谱。通过在PDGF-B-/-和PDGFR β-/-微血管中最下调的基因中鉴定已知的周细胞标志物来验证该方法。在新的周细胞标志物的候选者中，我们选择了ATP敏感的钾通道Kir6.1（也称为Kcnj 8）和磺酰脲受体2（SUR 2，也称为Abcc 9），这两个部分相同的通道复合物，以及δ同源物1（DLK 1）进行原位杂交，这表明它们在小鼠胚胎的脑周细胞中特异性表达。我们还发现Kir6.1在大脑的周细胞中高度表达，但在皮肤和心脏的周细胞中检测不到。这三种新的脑周细胞标记物是涉及离子转运和细胞间信号传导的信号分子，可能为脑微血管中周细胞功能打开新的窗口。
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 (PDGFR beta)-/- mouse mutants. The approach was validated by the identification of known pericyte markers among the most down-regulated genes in PDGF-B-/- and PDGFR beta-/- 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.