Permanently Re-programmed Microglia in Spinal Cord Injury Contribute to Functional Recovery

Microglia are resident myeloid cells of the central nervous system (CNS). Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated subtype of 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). As a consequence of SCI, homeostatic microglia undergo permanent transcriptional re-programming into a subtype of microglia with striking similarities to previoysly 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 homeostatic microglia and strongly enhance recovery of hind limb locomotor function following injury. Overall design: Investigation of CD45+ immune cells in spinal cord injury (SCI) over time in an experimental mouse model