High-dimensional imaging mass cytometry reveals diverse macrophage populations in human dorsal root ganglia (DRG). Microglia-like cells, characterized by markers such as P2RY12, SLC2A5, and TMEM119, localize near neuronal structures, whereas other myeloid subsets are found in interstitial regions. Spatial analysis reveals distinct localization patterns within the DRG.
ABSTRACT
The human dorsal root ganglia (DRG) are increasingly recognized as immunologically active sites within the peripheral nervous system. While single-cell transcriptomics has recently identified myeloid populations with microglia-like profiles in DRG across species, an in-depth, spatially resolved protein-level characterization in human tissue is lacking. Here, we used highly multiplexed Imaging Mass Cytometry (IMC) to map and phenotype myeloid cells in human DRG at subcellular resolution. A 41-marker panel enabled in-depth profiling of immune and neural cell types in situ. We identified a subset of Iba1+ myeloid cells co-expressing canonical microglial markers such as P2RY12, TMEM119, and SLC2A5, located in close spatial proximity to neuronal somata. Unsupervised clustering (FlowSOM) of >6000 Iba1+ cells identified eight distinct clusters. Among them, distinct myeloid cell subsets exhibited a clear microglial-like signature and were localized near neurofilament+ neurons. In contrast, Iba1+ clusters expressing CD68, HLA-DR, and other activation markers were spatially segregated. These findings provide a spatially resolved, protein‑level atlas of Iba1+ myeloid subsets in human DRG and offer a resource for dissecting neuroimmune niches relevant to chronic pain and peripheral neuropathies.