Single-nucleus analysis of intact spinal cord and spared tissue after complete injury in rhesus monkey

The lumbar spinal cord is fundamental for hindlimb function and serves as spared tissue after spinal cord injury (SCI). However, our knowledge about cellular heterogeneity of the intact spinal cord and spared tissues is still scarce especially in primates. Here, we used single-nucleus RNA sequencing analysis in rhesus monkey to characterize the cellular heterogeneity of the spinal cord and profile the dynamic changes of cells in spared tissues after complete thoracic SCI. We found that rhesus monkey and mice shared a highly conserved pattern of cellular constitution but with divergent gene expression. After SCI, the cellular characteristics of spared tissue changed permanently and showed a regionally diverse response. We identified an emerging oligodendrocyte subtype that responded to interferon and a new permanently activated microglia subtype that was responsible for eliminating cell debris. Overall, our findings revealed dynamic changes of cells in spared tissue, providing comprehensive insights for SCI repair. Overall design: Single-nucleus RNA-seq analysis of rhesus monkey spinal cord and spared lumbar spinal cord after complete injury.