A new fate mapping system reveals context-dependent random or clonal expansion of microglia
A new fate mapping system reveals context-dependent random or clonal expansion of microglia
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DOI：
10.1038/nn.4547
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发表时间：
2017-06-01
影响因子：
25
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
--
作者：
Tay, Tuan Leng;Mai, Dominic;Prinz, Marco
小胶质细胞构成了一个高度特化的组织驻留免疫细胞网络，对于控制组织稳态和解决CNS疾病非常重要。很少有人知道它们的空间分布是如何建立和维持在体内。在这里，我们建立了一个新的荧光命运映射系统来监测小胶质细胞在稳态和疾病期间的动态。我们的研究结果表明，小胶质细胞建立了一个密集的网络与区域差异，高区域周转率发现挑战小胶质细胞寿命的普遍概念。小胶质细胞在稳态条件下的自我更新构成了一个随机过程。在病理过程中，这种随机性转移到选择的克隆小胶质细胞扩增。在消退阶段，过量的疾病相关的小胶质细胞通过细胞流出和凋亡的双重机制被去除，以重建稳定的小胶质细胞网络。这项研究揭示了健康和患病CNS中成熟小胶质细胞的动态但离散的自组织。
Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity. Microglial self-renewal under steady state conditions constitutes a stochastic process. During pathology this randomness shifts to selected clonal microglial expansion. In the resolution phase, excess disease-associated microglia are removed by a dual mechanism of cell egress and apoptosis to re-establish the stable microglial network. This study unravels the dynamic yet discrete self-organization of mature microglia in the healthy and diseased CNS.