Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module
Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module
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DOI：
10.1038/s41593-019-0497-x
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发表时间：
2019-11-01
影响因子：
25
通讯作者：
Daneman, Richard
中科院分区：
文献类型：
--
作者：
Munji, Roeben Nocon;Soung, Allison Luen;Daneman, Richard
中枢神经系统中的血管形成一个专门的和关键的结构，血脑屏障（BBB）。我们提出了一个资源，以了解在健康和疾病过程中的功能障碍，调节血脑屏障功能的分子机制。利用内皮细胞富集和RNA测序，我们分析了小鼠内皮细胞的基因表达，比较脑内皮细胞和外周内皮细胞。我们还评估了脑卒中、多发性硬化、创伤性脑损伤和癫痫发作模型中CNS内皮基因表达的调节，每种模型都有深刻的BBB破坏。我们发现，虽然每一个是由不同的触发引起的，但它们在BBB破坏期间表现出惊人相似的内皮基因表达变化，包括将CNS内皮细胞转变为外周内皮细胞样状态的核心BBB功能障碍模块。BBB功能障碍的共同途径的鉴定表明，靶向治疗剂以限制它可能在多种神经系统疾病中有效。
Blood vessels in the CNS form a specialized and critical structure, the blood-brain barrier (BBB). We present a resource to understand the molecular mechanisms that regulate BBB function in health and dysfunction during disease. Using endothelial cell enrichment and RNA sequencing, we analyzed the gene expression of endothelial cells in mice, comparing brain endothelial cells with peripheral endothelial cells. We also assessed the regulation of CNS endothelial gene expression in models of stroke, multiple sclerosis, traumatic brain injury and seizure, each having profound BBB disruption. We found that although each is caused by a distinct trigger, they exhibit strikingly similar endothelial gene expression changes during BBB disruption, comprising a core BBB dysfunction module that shifts the CNS endothelial cells into a peripheral endothelial cell-like state. The identification of a common pathway for BBB dysfunction suggests that targeting therapeutic agents to limit it may be effective across multiple neurological disorders.