Cellular and molecular mechanisms of blood-brain barrier formation and maintenance

血脑屏障形成和维持的细胞和分子机制

• 批准号: 391580220
• 负责人: Professor Dr. Ralf H. Adams
• 金额: --
• 依托单位: National Natural Science Foundation of China
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/391580220?language=en
• 关键词: Cellular; molecular; mechanisms; blood; brain

Blood vessels in the brain need to provide adequate oxygen and nutrient supply, transport hormones and other signaling molecules, and remove waste products. At the same time, the brain vasculature prevents the entry of potentially harmful substances and immune cells from the circulation and thereby protects the functionality of neuronal networks. This blood-brain barrier, which involves tight interactions between endothelial cells, pericytes and astrocytes, is critical for the healthy organism and, accordingly, its breakdown is a hallmark of numerous human diseases such as stroke, neurodegeneration and multiple sclerosis. Despite of the great importance of the blood-brain barrier, the underlying molecular regulation remains little understood. Here, we propose to use a combination of sophisticated mouse genetics, RNA sequencing, analysis of chromatin modifications, cell co-culture experiments, and functional in vivo assays to resolve several key questions regarding blood-brain barrier formation and maintenance. In particular, our joint research program will address molecular principles of pericyte recruitment and plasticity, the regulation of the brain endothelium by the transporter Mfsd2a, and the interplay between pericytes and endothelial cells.

大脑中的血管需要提供足够的氧气和营养供应，运输激素和其他信号分子，并清除废物。同时，脑血管系统防止潜在有害物质和免疫细胞进入血液循环，从而保护神经网络的功能。这种血脑屏障涉及内皮细胞、周细胞和星形胶质细胞之间的紧密相互作用，对健康的有机体至关重要，因此，它的崩溃是许多人类疾病的标志，如中风、神经退行性变和多发性硬化症。尽管血脑屏障非常重要，但其潜在的分子调控机制仍鲜为人知。在这里，我们建议结合复杂的小鼠遗传学、RNA测序、染色质修饰分析、细胞共培养实验和体内功能分析来解决有关血脑屏障形成和维护的几个关键问题。特别是，我们的联合研究计划将涉及周细胞招募和可塑性的分子原理，转运蛋白Mfsd2a对脑内皮细胞的调节，以及周细胞和内皮细胞之间的相互作用。

项目成果

A molecular map of murine lymph node blood vascular endothelium at single cell resolution

• DOI: 10.1038/s41467-020-17291-5
• 发表时间: 2020-07-30
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Brulois, Kevin;Rajaraman, Anusha;Butcher, Eugene C.
• 通讯作者: Butcher, Eugene C.

Genetic Lineage Tracing of Nonmyocyte Population by Dual Recombinases

双重组酶对非肌细胞群的遗传谱系追踪

• DOI: 10.1161/circulationaha.118.034250
• 发表时间: 2018-08-21
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Li, Yan;He, Lingjuan;Zhou, Bin
• 通讯作者: Zhou, Bin

Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury

• DOI: 10.1016/j.stem.2019.10.006
• 发表时间: 2019-12-05
• 期刊: CELL STEM CELL
• 影响因子: 23.9
• 作者: Chen, Qi;Liu, Yang;Adams, Ralf H.
• 通讯作者: Adams, Ralf H.

Donor cell memory confers a metastable state of directly converted cells.

供体细胞记忆赋予直接转化细胞亚稳态

• DOI: 10.1016/j.stem.2021.02.023
• 发表时间: 2021
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Kim KP;Bunina D;Jeong HW;Ghelman J;Yoon J;Shin B;Park H;Han DW;Zaugg JB;Kuhlmann T;Adams RH;Noh KM;Goldman SA;Schöler HR
• 通讯作者: Schöler HR