Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration

Published: 14 February 2023| Version 1 | DOI: 10.17632/rh82z6vsxt.1
Rui Feng, Vishnu Muraleedharan Saraswathy, Mayssa Mokalled, Valeria Cavalli


Resource raw data for manuscript Abstract: Sensory neurons located in dorsal root ganglia (DRG) convey sensory information from peripheral tissue to the brain. After peripheral nerve injury, sensory neurons switch to a regenerative state to enable axon regeneration and functional recovery. This process is not cell autonomous and requires glial and immune cells. Macrophages in the DRG (DRGMacs) accumulate in response to nerve injury, but their origin and function remains unclear. Here we mapped the fate and response of DRGMacs to nerve injury using macrophage depletion, fate-mapping and single-cell transcriptomics. We identified three subtypes of DRGMacs after nerve injury in addition to a small population of circulating bone-marrow-derived precursors. Self-renewing macrophages, which proliferate from local resident macrophages, represent the largest population of DRGMacs. The other two subtypes include microglia-like cells and macrophage-like satellite glial cells (Imoonglia). We show that self-renewing DRGMacs contribute to promote axon regeneration. Using single-cell transcriptomics data and CellChat to simulate intercellular communication, we reveal that macrophages express the neuroprotective and glioprotective ligand prosaposin and communicate with satellite glial cells via the prosaposin receptor GPR37L1. These data highlight that DRGMacs have the capacity to self-renew, similarly to microglia in the CNS and contribute to promote axon regeneration. These data also reveal the heterogeneity of DRGMacs and their potential neuro- and glioprotective roles, which may inform future therapeutic approaches to treat nerve injury.