Single-nucleus RNA sequencing identified cells with ependymal cell-like features enriched in neonatal mice after spinal cord injury

The adult mammalian central nervous system has limited regenerative ability, and spinal cord injury (SCI) often causes lifelong motor disability. While regeneration is limited in adults, injured spinal cord tissue can be re-generated and neural function can be almost completely restored in neonates. However, difference of cellular composition in lesion has not been well characterized. To gain insight into the age-dependent cellular reaction after SCI, we performed single-nucleus RNA sequencing, analyzing 4076 nuclei from sham and injured spinal cords from adult and neonatal mice. Clustering analysis identified 18 cell populations. We identified previously undescribed cells with ependymal cell-like gene expression profile, the number of which was increased in ne-onates after SCI. Histological analysis revealed that these cells line the central canal under physiological con-ditions in both adults and neonates. We confirmed that they were enriched in the lesion only in neonates. We further showed that these cells were positive for the cellular markers of ependymal cells, astrocytes and radial glial cells. This study provides a deeper understanding of neonate-specific cellular responses after SCI, which may determine regenerative capacity.

Automated summary

The regenerative ability of the adult mammalian central nervous system is limited, while spinal cord injuries often lead to lifelong motor disabilities. However, neonates have the potential to regenerate and restore neural function. This study used single-nucleus RNA sequencing to analyze the cellular composition in injured spinal cords of adult and neonatal mice. The results revealed previously undescribed cells with ependymal cell-like gene expression profiles, which were found to be enriched only in neonates after injury. These findings provide a deeper understanding of the cellular responses specific to neonates after spinal cord injury, which may play a role in determining regenerative capacity.