GSE195437
Specification of CNS macrophage subsets occurs postnatally in defined anatomical niches
All tissue resident macrophages of the central nervous system (CNS), including parenchymal microglia as well as CNS-associated macrophages (CAMs) such as meningeal (mMF) and perivascular macrophages (pvMF) are part of the CNS endogenous innate immune system that acts as the first line of defense during infections or trauma. It has been suggested that microglia and all CAM subsets are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAMs subsets in situ are poorly understood. Using novel fate mapping systems, single-cell profiling and cell-specific mutants, we show that only mMF and microglia share a common prenatal progenitor. In contrast, pvMF originate from perinatal mMF only after birth in an integrin-dependent manner. Furthermore, the establishment of pvMF? critically requires the presence of vascular smooth muscle cells. In summary, our data reveal a novel precisely timed process in distinct anatomical niches for the establishment of CNS macrophage subsets. Overall design: A1/A2 cells were FACS-sorted, from extraembryonic YS at E9.5 into a 384-well (Bio-Rad Laboratories, Munich, Germany) plate containing lysis buffer and barcodes. The gating strategies for FACS-sorting, related to the datasets shown in Fig. 2a-d, Extended Data Fig. 5b-d, were shown in Extended Data Fig. 5a.