GSE128781
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. [bulk RNA-Seq]
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less 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 capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested 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 the healthy and diseased brain. Overall design: 4 replicates of ME-MHCII-high, 4 replicates of ME-MHCII-int, 4 replicates of PM, 4 replicates of NCPM and 4 replicates of NMG. We compared these samples with the AMF Cre- and KC Cre- samples of GSE117081