While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.

中文翻译：

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小鼠脑巨噬细胞的单细胞图谱揭示了由个体发育和组织环境塑造的独特转录特征。

虽然实质小胶质细胞在脑内稳态和疾病中的作用相当清楚，但其他大脑驻留骨髓细胞仍然不太了解。通过解剖边界区域并将单细胞 RNA 测序与高维细胞术、大量 RNA 测序、命运图谱和显微镜相结合，我们揭示了非实质脑巨噬细胞的多样性。位于硬脑膜、硬膜下脑膜和脉络丛中的边界相关巨噬细胞 (BAM) 由具有组织特异性转录特征的不同亚群组成，并且它们的细胞组成在出生后发育过程中发生了变化。BAM 表现出混合的个体发育，并且子集在耗尽和重新繁殖后表现出明显的自我更新能力。单细胞和命运图分析均表明存在一个独特的小胶质细胞亚群位于脉络丛上皮的顶端表面。最后，基因网络分析和条件性删除揭示了 IRF8 作为驱动脑巨噬细胞成熟和多样性的主要调节因子。我们的结果为理解健康和患病大脑中的宿主-巨噬细胞相互作用提供了一个框架。