Single-nucleus transcriptomic atlas of glial cells in human dorsal root ganglia

Abstract

Abstract Purpose Glial cells play a crucial role in regulating physiological and pathological functions, such as sensation, infections, acute injuries, and chronic neurodegenerative disorders. Despite the recent understanding of glial subtypes and functional heterogeneity in central nervous system via single-cell/nucleus RNA sequencing, the transcriptomic profiles of glial cells in the adult human dorsal root ganglia (DRG) have not yet been characterized at single-cell resolution. Methods We used high-throughput single-nucleus RNA sequencing to map the cellular and molecular heterogeneity of satellite glial cells (SGCs) and Schwann cells (SCs) in the human DRG, and further compared these human findings with those from mice. The expression profiles of classical marker genes of peripheral somatosensory system in glial cells were examined in human and mouse DRG. Additionally, the functional properties of the enriched genes in glial cells and their subtypes were also explored by Gene Ontology (GO) term analysis. Results Human DRG cells were initially classified into 11 clusters based on their distinct transcriptional characteristics. SGCs and SCs were identified through their representative marker genes. SGCs were further classified into six subclusters, while SCs were classified into seven subclusters. The comparison with mouse transcriptomic profiles revealed an overall similarity between the two species, while simultaneously highlighting some degree of heterogeneity in specific genes. Conclusions This atlas comprehensively profiled glial cell heterogeneity and provides a powerful resource for investigating the cellular basis of physiological and pathological conditions associated with DRG glial cells. Graphical Abstract