A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair

Matson, K. J.; Russ, D. E.; Kathe, C.; Maric, D.; Hua, I.; Krynitsky, J.; Pursley, R.; Sathyamurthy, A.; Squair, J. W.; Courtine, G.; Levine, A. J.

doi:10.1101/2021.04.28.441862

bioRxiv · 10.1101/2021.04.28.441862

A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair

Matson, K. J.·Russ, D. E.·Kathe, C.·Maric, D.·Hua, I.·Krynitsky, J.·Pursley, R.·Sathyamurthy, A.·Squair, J. W.·Courtine, G.·Levine, A. J.

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Abstract

After spinal cord injury (SCI), the "spared" tissue below the lesion contains undamaged cells that could support or augment recovery, but targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we used single nucleus sequencing to profile how each cell type in the lumbar spinal cord changes over time after a thoracic injury. We present an atlas of these dynamic responses and explore two unexpected findings. Amongst neurons, rare cell types expressed a molecular signature of regeneration and amongst microglia, we identified a population of "trauma associated microglia" (TAM). These TAM cells were present in the white matter near degenerating axons and expressed the trophic factors Igf1 and Spp1(OPN). Viral over-expression of Igf1 and Spp1(OPN) expanded the TAM population and promoted the clearance of myelin debris. These findings expose endogenous mechanisms of repair in spared neural tissue, uncovering potential candidates for targeted therapy.

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Matson, K. J., Russ, D. E., Kathe, C., Maric, D., Hua, I., Krynitsky, J., Pursley, R., Sathyamurthy, A., Squair, J. W., Courtine, G., Levine, A. J.. 2021-04-29. A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair. https://doi.org/10.1101/2021.04.28.441862

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