Peripheral Neuropathy Research Group, Department of Biomedical Sciences, Institute Born Bunge, University of Antwerp, Antwerp, Belgium.
VIB Center for Inflammation Research, Ghent, Belgium.
Nat Neurosci. 2020 May;23(5):676-689. doi: 10.1038/s41593-020-0618-6. Epub 2020 Apr 13.
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: RelmαMgl1 snMacs in the epineurium and RelmαMgl1 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.
虽然中枢神经系统（CNS）小胶质细胞已经得到了广泛的研究，但对于分布在周围神经系统中的巨噬细胞知之甚少。在这里，我们对坐骨神经巨噬细胞（snMac）进行了发生、转录组和空间特征分析。使用多种命运映射系统，我们表明 snMac 并非源自早期胚胎期在 CNS 中定植的前体细胞，而是主要来源于晚期胚胎期前体细胞，并随着时间的推移被骨髓来源的巨噬细胞取代。通过单细胞转录组学，我们鉴定出 snMac 的组织特异性核心特征和两个空间分离的 snMac：位于神经外膜的 RelmαMgl1 snMac 和位于神经内膜的 RelmαMgl1 snMac。总体而言，snMac 缺乏小胶质细胞核心特征基因的大部分，只有神经内膜亚群表达这些基因中的少数。在神经损伤时，这两种驻留的 snMac 群体表现出不同的反应。此外，与 CNS 不同的是，在损伤过程中发育的单核细胞衍生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。
