Transcriptomic Profiling Reveals Injury Responses of Peripheral Glial Cells in Sensory Neuron Microenvironment

Schwann cells and satellite glial cells (SGCs) are important peripheral glial cells in the dorsal root ganglion (DRG) and commendable participants in regulating neuronal functions. Herein, through re-analysis of publicly available single-nucleus RNA sequencing data from naïve and injured DRG at 1 and 3 days following sciatic nerve crush, we systematically characterized the transcriptomic alterations in Schwann cells and SGCs. Cell clustering and counting showed that peripheral glial cells occupied a large population after sciatic nerve crush injury. Using differentially expression analysis, we found that apoptosis and immune responses were involved in all these examined peripheral glial cells. Unique glial cells also responded differently to sciatic nerve crush injury, with myelinating Schwann cells characterized by enriched adenosine 5'-monophosphate activated protein kinase (AMPK) metabolic signaling, non-myelinating Schwann cells characterized by enriched tissue-remodeling-related signaling, and SGCs characterized by enriched ion channels. Using single-cell regulatory network inference and clustering (SCENIC) to determine essential transcription factors in specific cell type at the naïve state and at multiple time points after sciatic nerve crush injury, we found that Schwann cells and SGCs possessed their own elevated transcription factor-coding genes, with activating factor 3 (Atf3) commonly highly up-regulated in all peripheral glial cells. This study provides a profiling map of peripheral glial cells at the naïve and injured states, expands the acknowledgment of the molecular background of nerve injury, and can lead to novel strategies to promote sensory nerve regeneration.