德国弗莱堡大学Marco Prinz和Takahiro Masuda研究组合作取得一项新成果。他们开发出了用于研究中枢神经系统（CNS）小胶质细胞的基于己糖胺半乳糖苷酶亚基β（Hexb）的新颖工具。相关论文发表在2020年6月15日出版的《自然-免疫学》杂志上。

为了开发新的小胶质细胞基因靶向模型，他们首先应用大规模平行单细胞分析来比较稳态和疾病期间的小胶质细胞和CNS相关的巨噬细胞（CAM）特征，并确定Hexb是稳定表达的小胶质细胞核心基因，而其他小胶质细胞核心基因是在病理过程中被大幅下调。接下来，他们构建HexbtdTomato小鼠以稳定地监测体内的小胶质细胞行为。

最后，将Hexb基因座用于小胶质细胞中他莫昔芬诱导的Cre介导的基因操作，以及小胶质细胞的命运定位，而不是CAM。总之，他们提供了有价值的新遗传工具来专门研究中枢神经系统中的小胶质细胞功能。

据介绍，小胶质细胞和CAM，例如血管周围和脑膜巨噬细胞，实际上与所有CNS疾病有关。但是，在缺乏合适的工具以区分个体上紧密相关的小胶质细胞和CAMs的功能方面，关于它们对细胞类型的特定作用知之甚少。

附：英文原文

Title: Novel Hexb-based tools for studying microglia in the CNS

Author: Takahiro Masuda, Lukas Amann, Roman Sankowski, Ori Staszewski, Maximilian Lenz, Paolo dErrico, Nicolas Snaidero, Marta Joana Costa Jordo, Chotima Bttcher, Katrin Kierdorf, Steffen Jung, Josef Priller, Thomas Misgeld, Andreas Vlachos, Melanie Meyer Luehmann, Klaus-Peter Knobeloch, Marco Prinz

Issue&Volume: 2020-06-15

Abstract: Microglia and central nervous system (CNS)-associated macrophages (CAMs), such as perivascular and meningeal macrophages, are implicated in virtually all diseases of the CNS. However, little is known about their cell-type-specific roles in the absence of suitable tools that would allow for functional discrimination between the ontogenetically closely related microglia and CAMs. To develop a new microglia gene targeting model, we first applied massively parallel single-cell analyses to compare microglia and CAM signatures during homeostasis and disease and identified hexosaminidase subunit beta (Hexb) as a stably expressed microglia core gene, whereas other microglia core genes were substantially downregulated during pathologies. Next, we generated HexbtdTomato mice to stably monitor microglia behavior in vivo. Finally, the Hexb locus was employed for tamoxifen-inducible Cre-mediated gene manipulation in microglia and for fate mapping of microglia but not CAMs. In sum, we provide valuable new genetic tools to specifically study microglia functions in the CNS.

DOI: 10.1038/s41590-020-0707-4

Source: https://www.nature.com/articles/s41590-020-0707-4