Do microglia exist in the peripheral nervous system?

It is widely accepted that microglia are present in the central nervous system (CNS) but not in the peripheral nervous system (PNS).1,2 However, this notion is challenged by a recent study published in Cell.3 Wu et al. discovered microglia-like cells that envelop the neuronal soma in the PNS, specifically in the dorsal root ganglion (DRG) and sympathetic ganglion (SG). These microglia-like cells share transcriptomic and epigenetic profiles with CNS microglia and play a key role in regulating the neuronal soma sizes in the DRG and SG. Notably, PNS microglia-like cells have been identified in primates (humans and macaques) and large-body-sized animals (e.g., pigs) but are absent in small-body-sized animals, such as rodents (mice and rats).3 This absence underscores the limitations of using rodent models to study human diseases.

Wu et al. provided several lines of evidence to support the existence and function of microglia-like cells in the PNS (Figures 1A and 1B). First, single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses of the DRG and SG revealed that these cells express core microglial signature genes, including P2RY12, TMEM119, and SALL1, while lacking classical macrophage markers (MRC1, DAB2, and LYVE1). Additionally, these PNS microglia-like cells share both transcriptomic and epigenetic profiles with CNS microglia, as demonstrated by ATAC-seq and chromatin immunoprecipitation (ChIP)-seq analyses.