TY - JOUR
T1 - Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration
AU - Feng, Rui
AU - Saraswathy, Vishnu Muraleedharan
AU - Mokalled, Mayssa H.
AU - Cavalli, Valeria
N1 - Funding Information:
kindly providing the PLX73086 and PLX5622 compound and formulated diet. We show our gratitude and respect to all animals killed in this study. This work was funded in part by NIH grants R35 NS122260, R01 NS111719 and R21 NS115492 to V.C.
Funding Information:
We would like to thank members of the Cavalli lab and Mokalled lab for valuable discussions and suggestions. We thank Dr. Qingyun Li and Dr. Jonathan Kipnis for constructive discussion and comments. We gratefully acknowledge Michael Savio from The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine for assistance with single-cell sorting. We would like to thank Plexxikon Inc for kindly providing the PLX73086 and PLX5622 compound and formulated diet. We show our gratitude and respect to all animals killed in this study. This work was funded in part by NIH grants R35 NS122260, R01 NS111719 and R21 NS115492 to V.C.
Publisher Copyright:
Copyright © 2023 the Author(s).
PY - 2023/2/14
Y1 - 2023/2/14
N2 - 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 remain 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 (SGCs) (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 SGCs via the prosaposin receptor GPR37L1. These data highlight that DRGMacs have the capacity to self-renew, similarly to microglia in the Central nervous system (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.
AB - 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 remain 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 (SGCs) (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 SGCs via the prosaposin receptor GPR37L1. These data highlight that DRGMacs have the capacity to self-renew, similarly to microglia in the Central nervous system (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.
KW - axon regeneration
KW - dorsal root ganglion (DRG)
KW - macrophages
KW - peripheral nerve injury
KW - satellite glial cells (SGCs)
UR - http://www.scopus.com/inward/record.url?scp=85147894353&partnerID=8YFLogxK
U2 - 10.1073/pnas.2215906120
DO - 10.1073/pnas.2215906120
M3 - Article
C2 - 36763532
AN - SCOPUS:85147894353
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
M1 - e2215906120
ER -