A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

Hannah Van Hove, Liesbet Martens , Isabelle Scheyltjens, Karen De Vlaminck, Ana Rita Pombo Antunes, Sofie De Prijck, Niels Vandamme, Sebastiaan De Schepper , Gert Van Isterdael, Charlotte L. Scott, Jeroen Aerts, Geert Berx, Guy E. Boeckxstaens, Roosmarijn E. Vandenbroucke, Lars Vereecke, Diederik Moechars, Martin Guilliams, Jo Van Ginderachter, Yvan Saeys, Kiavash Movahedi

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1021-1035
Number of pages15
JournalNature Neuroscience
Volume22
Issue number6
DOIs
Publication statusPublished - 6 May 2019

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