Distinct signature, origin and dynamics of macrophages in the peripheral and central nervous system (microarray)

We performed ontogenic, transcriptomic and spatial characterization of sciatic nerve Macs (snMacs). Using multiple fate-mapping systems, we show that snMacs do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursors and get replaced by bone marrow-derived Macs over time. Using single-cell profiling, we identified a tissue-specific core signature of snMacs and found two spatially-separated snMacs: Relmα + Mgl1 + snMacs in the epineurium and Relmα Mgl1 snMacs in the endoneurium. Globally, snMacs lack most core signature genes of microglia, with only the endoneurial subset expressing a restricted number of these genes. Single-cell transcriptomics revealed that in response to injury both snMacs respond differently and that the PNS, in contrast to the CNS, is permissive to prolonged engraftment of monocyte-derived Macs recruited upon injury. Microarray = Sciatic Nerve macrophages in steady state and different time points (1.5, 5, 10 and 37 days) after nerve crush. This data was compared to previously published data (GSE75225 and GSE117080) and to other tissue resident macrophages from the Immgen Consortium Database (GSE15907). Bulk RNA Seq = Brain microglia, Optic Nerve macrophages and Sciatic Nerve macrophages. For each cell type there are 4 replicates, expect for the Brain microglia there are 5 replicates. Single cell RNA Seq = on steady state Sciatic Nerve macrophages and at different time points (1 day and 5 days) after nerve crush.