Single-cell atlas of brain-resident macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

Mammal brains are inhabited by a myriad of myelod cells, a good part of which is represented by resident parenchymal microglia, the homeostatic role of which, in the brain, has been abundantly investigated in the last decades. On the other hand, other brain-resident myeloid lineages, usually located at the outer interface regions of the central nervous system (CNS) have still been poorly characterized, and their involvement in brain homeostasis largely unknown. In this paper, recently published by Hannah Van Hove and collaborators on Nature Neuroscience, the authors characterized the trascriptional fingerprint, phenotype and ontogeny of monocyte subsets that reside in different non-parenchymal brain compartments.

Border-associated macrophages (BAM) represent a wide spectrum of innate immune cells that are located in the perivascular spaces, meninges and choroid plexus of the CNS, which display different phenotypes and ontogeny. By means of RNA-seq and high-dimensional fluorescence cytometry, the authors could compile a complete profile that individuated recurrent – although distinct – BAM-related transcriptional and protein signatures that depended on the brain region inhabited by each subset. The authors initially individuated six BAM subsets that inhabit in non-parenchymal brain regions: two dural-residing subsets (characterized by differential MHCII expression), a sub-dural set and three distinct macrophage populations that are located in the choroid plexus, all of which possibly sharing microglial ontogeny as suggested by their partial expression of microglial markers. Starting from this, the authors narrowed the analysis of the subsets and went deeper in characterizing the BAM transcriptional core signature in order to individuate tissue-specific adaptation and development, neurodegenerative potential, as well as specific transcription factors of these interface macrophages.

Source: Nature Neuroscience

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