The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells.

The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells.
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DOI:
10.1371/journal.pone.0013741
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发表时间:
2010-10-29
期刊:
影响因子:
3.7
通讯作者:
Barres BA
Barres BA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Daneman R;Zhou L;Agalliu D;Cahoy JD;Kaushal A;Barres BA

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血脑屏障(BBB)维持大脑内环境平衡,限制毒素和病原体进入大脑。尽管它很重要,但人们对调节这一关键屏障的发展和功能的分子机制知之甚少。在这项研究中,我们开发了从不同组织中高度纯化内皮细胞和基因图谱的方法,并通过比较脑内皮细胞的转录图谱与从肝脏和肺中纯化的转录图谱,我们产生了丰富的转录物资源,这些转录物富含在形成脑内皮细胞的血脑屏障中。通过这种比较,我们发现了在中枢神经系统(CNS)内皮细胞中表达丰富的新的紧密连接蛋白、转运蛋白、代谢酶、信号成分和未知转录本。这一分析已经确定RXRpha信号级联在血脑屏障中特异性地富含,暗示这一途径参与调节这一重要的屏障。该数据集为了解中枢神经系统内皮细胞及其与神经和血细胞的相互作用提供了资源。
The blood-brain barrier (BBB) maintains brain homeostasis and limits the entry of toxins and pathogens into the brain. Despite its importance, little is known about the molecular mechanisms regulating the development and function of this crucial barrier. In this study we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are enriched in the BBB forming endothelial cells of the brain. Through this comparison we have identified novel tight junction proteins, transporters, metabolic enzymes, signaling components, and unknown transcripts whose expression is enriched in central nervous system (CNS) endothelial cells. This analysis has identified that RXRalpha signaling cascade is specifically enriched at the BBB, implicating this pathway in regulating this vital barrier. This dataset provides a resource for understanding CNS endothelial cells and their interaction with neural and hematogenous cells.
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