Proceedings of AIM-SCI 2025: Azores International Meeting on Spinal Cord Injury

Our lab has recently shown that Acomys dimidiatus (Muridae family) is a unique mammal capable of repairing the spinal cord after complete transection, with remarkable functional recovery.Our initial analyses revealed that this outcome is associated with a pro-regenerative ECM formed at the lesion site, in which high levels of the 3gnt7 enzyme lead to increased keratan sulfate proteoglycan (KSPG) deposition.While this ECM signature is essential for repair, longitudinal bulk transcriptomics revealed that a critical transcriptional switch occurs earlier.In both Acomys and Mus musculus (non-regenerative species), inflammation and fibrosis are activated early after spinal cord injury (SCI).However, in Acomys, these are then downregulated, and followed by activation of gene networks supporting axon growth and synaptogenesis.By contrast, Mus has sustained activation of inflammation and fibrosis, and repression of neuroregenerative programs.This supports that in Acomys, an initial scar-forming response facilitates wound closure but is subsequently resolved to allow regeneration.To elucidate the cellular populations enabling this switch, we generated a single-nucleus RNAseq/ATACseq atlas of the SCI site of both species.Our data identified specific microglial subpopulations as possible key mediators of spinal cord regeneration in Acomys.Moreover, it showed that microglia is the 3gnt7-expressing cell after lesion.These findings laid the foundation to explore the role of specific microglia subpopulations in the regenerative ability of Acomys, including the ongoing generation of Acomys-like Mus models over-expressing 3gnt7 in microglia.These experiments will pave the way for developing microglia-targeted and KSPG-based therapies to promote spinal cord repair in patients.