Establishing a Spatio-Temporal Atlas of Gene Expression after Traumatic Spinal Cord Injury

Abstract

Traumatic spinal cord injury (tSCI) has no cure, and effective treatments will require targeting secondary injury mechanisms at specific times and locations. This demands understanding how gene expression changes across space and time. Previous transcriptomic studies lack spatial context due to tissue homogenization. To overcome this, spatial transcriptomics was applied to characterize spinal cord gene regulation after tSCI. Female Thy1-YFP mice (14–16 weeks) received moderate T12 contusion injuries and were sacrificed at 4 hours, 48 hours, and 7 days, with a naïve control. Coronal and longitudinal sections were analyzed using the 10x Genomics® Visium HD platform. Graph-based clustering, spatially variable gene detection, differential expression, cell-type deconvolution, and ligand-receptor analysis revealed region-specific patterns among ~16,500 genes. Neuronal and glial genes decreased, while transcription factors and immune-related genes increased. Egr1, Spp1, and Apoe showed dynamic spatiotemporal responses. Findings highlight spatial transcriptomics as a powerful tool to guide development of targeted SCI therapies.