While central nervous system (CNS) microglia have been studied extensively, surprisingly little is known about macrophages populating the peripheral nervous system (PNS Macs). 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.
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Here you can find the scripts used to analyse all the data:
- script_analysisFig1.R = Compare sciatic nerve macrophages to brain microglia, alveolar macrophages, liver Kupffer cells, peritoneal macrophages and splenic red pulp macrophages
- script_analysisFig2.R = Compare sciatic nerve macrophages to brain microglia and optice nerve macrophages.
- script_analysisFig4.R = Compare steady state sciatic nerve macrophages with sciatic nerve macrophages on different time points after nerve crush.
- script_analysisFig5.R = Analysis of steady state sciatic nerve macrophage at single cell level.
- script_analysisFig6.R = Compare steady state sciatic nerve macrophages with sciatic nerve macrophages on different time points after nerve crush at single cell level.
- script_analysisSuppFig4.R = Analysis of the heterogeneity of central nervous system macrophages and peripheral nervous system macrophages.
Elke Ydens, Lukas Amann, Bob Asselbergh, Charlotte L. Scott, Liesbet Martens, Dorine Sichien, Omar Mossad, Thomas Blank, Sofie De Prijck, Donovan Low, Takahiro Masuda, Yvan Saeys, Vincent Timmerman, Ralf Stumm, Florent Ginhoux, Marco Prinz, Sophie Janssens and Martin Guilliams.Distinct signature, origin and dynamics of macrophages in the peripheral and central nervous system. Nature Neuroscience, 2020.