ScRNA analysis and ferroptosis-related ceRNA regulatory network investigation in microglia cells at different time points after spinal cord injury

Abstract

Spinal cord injuries (SCI) are usually caused by mechanical trauma that leads to serious physical and psychological damage to the patient as well as a huge economic burden to the whole society. The prevention, treatment, and rehabilitation of spinal cord injuries have become a major issue for the medical community today due to the enormous social and economic expenditure induced via spinal cord injuries. Therefore, in-depth research into SCI is necessary. Microglia have been shown to be the key player in the immune inflammatory response after spinal cord injury, but the mechanisms of immune regulation at different time points after spinal cord injury remain unclear. To investigate the inflammatory biomarkers associated with microglia at different time points after SCI, we downloaded single-cell RNA sequencing data from mouse spinal cords 3- and 14-days after the injury and identified subpopulations associated with microglia. Further functional enrichment analysis also confirmed that microglia are associated with immune system regulation at different time points and that both can modulate cytokine production. As ferroptosis is a newly identified non-apoptotic programmed cell death, microglia establish a bridge between ferroptosis and CNS inflammation and may play an important role in spinal cord injury. We then screened for genes differentially expressed in microglia during 3- and 14-days after spinal cord injury and associated with iron death, named Stmn1 and Fgfbr1, respectively, and verified that these pivotal genes are closely related to the immune cells. Finally, we also screened for drug fractions associated with these pivotal genes. Our results predict key genes in the immune inflammatory process associated with microglia at different time points after spinal cord injury at the single-cell level and provide a molecular basis for better treatment of SCI.

Keywords: Ferroptosis; Hub gene; Inflammation; Microglia; Single-cell analysis; Spinal cord injuries (SCI).