While CNS microglia have been extensively studied, relatively little is known about macrophages populating the peripheral nervous system. Here we performed ontogenic, transcriptomic and spatial characterization of sciatic nerve macrophages (snMacs). Using multiple fate-mapping systems, we show that snMacs do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursors and become replaced by bone-marrow-derived macrophages over time. Using single-cell transcriptomics, we identified a tissue-specific core signature of snMacs and two spatially separated snMacs: Relmα+Mgl1+ snMacs in the epineurium and Relmα-Mgl1- snMacs in the endoneurium. Globally, snMacs lack most of the core signature genes of microglia, with only the endoneurial subset expressing a restricted number of these genes. In response to nerve injury, the two resident snMac populations respond differently. Moreover, and unlike in the CNS, monocyte-derived macrophages that develop during injury can engraft efficiently in the pool of resident peripheral nervous system macrophages.

中文翻译：

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对周围神经巨噬细胞进行分析可发现两个巨噬细胞亚群，具有不同的定位，转录组和对损伤的反应。

尽管已经广泛研究了中枢神经系统小胶质细胞，但是对于巨噬细胞在周围神经系统中的分布知之甚少。在这里，我们进行了坐骨神经巨噬细胞（snMacs）的本体，转录组和空间表征。使用多个命运映射系统，我们显示snMacs并非源自殖民中枢神经系统的早期胚胎前体，而是主要源自晚期胚胎前体，并随着时间的流逝而被骨髓来源的巨噬细胞所取代。使用单细胞转录组学，我们确定了snMacs和两个空间上分离的snMacs的组织特异性核心特征：神经外膜中的Relmα+ Mgl1 + snMacs和神经内膜中的Relmα-Mgl1-snMacs。在全球范围内，snMacs缺乏小胶质细胞的大多数核心特征基因，只有神经内膜亚型表达有限数量的这些基因。对于神经损伤，两个常驻snMac群体的反应不同。而且，与中枢神经系统不同，在损伤过程中产生的源自单核细胞的巨噬细胞可以有效地植入驻留的周围神经系统巨噬细胞池中。