Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery

Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.

Automated summary

This study used single-cell RNA sequencing to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. It was found that baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with similarities to disease-associated microglia (DAM) and a distinct microglial state found during development. Depletion of microglia showed that DAM in SCI are derived from baseline microglia and enhance recovery of hindlimb locomotor function following injury.