An integrated single-cell atlas of peripheral glia reveals progenitor-like states and enables cross-study mapping of dorsal root ganglia

Abstract

Sensory ganglia in the peripheral nervous system contain diverse glial populations that modulate sensory signaling, respond to injury and contribute to tissue homeostasis. Satellite glial cells (SGCs) surrounding neuronal soma in dorsal root ganglia (DRG) were suggested to retain developmental potential, but the identity of progenitor cells remains undefined. To capture glial diversity, we assembled a comprehensive single-cell transcriptomic atlas by integrating over 200,000 DRG and sciatic nerve transcriptomes across multiple studies and injury paradigms. High-resolution clustering resolved 28 cell types and demonstrated significant transcriptional heterogeneity within SGCs and Schwann cells, including repair and reactive sub-states. We identified two distinct populations of progenitor cells that reflect different states in the progenitor trajectory. Functionally, progenitor cell numbers increase after injury, and endothelin signaling regulates glial cell proliferation early in development. This integrated DRG and peripheral nerve atlas represents an essential resource for exploring new features of the peripheral nervous system.