Spinal cord injury (SCI) can have severe and lasting effects on a person's ability to move, breathe, and perform daily activities. While there is no cure for SCI, treatment and rehabilitation can help manage symptoms and improve quality of life. A recent study published in the journal Cell Reports (Volume 42, Issue 5) aimed to understand the cellular heterogeneity of glial progenitor subpopulations in healthy and injured adult spinal cords.

The researchers used single-cell RNA sequencing to investigate the molecular diversity and dynamics of glial progenitor subpopulations in the spinal cords of adult mice with SCI. They found that the predominant cellular component of the scar after SCI was astrocytes, which play a crucial role in neural protection and repair. However, astrocytes also secrete inhibitory factors that may limit neuroregeneration, making it important to define the complex astroglia and astroglial precursor response to injury.

Cellular diversity and dynamics in spinal cord injury

The study identified seven astrocyte-lineage cell clusters and found intermediate populations that expressed both astrocyte and oligodendrocyte precursor cell marker genes, as well as genes associated with neuronal, immune, and proliferation markers. The researchers used gene set enrichment analysis to infer the functional characteristics of these subpopulations and found that different gene sets were significantly enriched in specific subpopulations/states.

The authors also used the single-cell regulatory network inference and clustering pipeline to identify potential master regulators that drive the cellular heterogeneity of astrocyte-lineage cell subpopulations/states. They found that there were subpopulation-specific master regulons, such as stemness and ependymal-related regulons in cluster 1, proliferation-related regulons in cluster 2, astrocyte-related regulons in cluster 3, and immune-related regulons in cluster 6.

Astrocyte-lineage cell clusters in both acute and sub-chronic SCI, insights into neural stem cells in spinal cord

Moreover, the researchers re-analyzed published scRNA-seq datasets of acute SCI stages and compared the astrocyte-lineage cell subpopulations with those found in sub-chronic SCI. They identified 12 astrocyte-lineage cell clusters, and found that most of the subpopulations/states in sub-chronic SCI were also present in the acute stages of SCI. Additionally, they evaluated the expression of gene sets related to cell-cycle stages and found that cells in cluster 3 and clusters 1 and 5 were in a proliferative phase, with their proportions increasing after injury.

The study provides insights into the molecular signature, location, and morphologies of potential resident neural stem cells or neural progenitor cells in the adult spinal cord. The findings suggest that GFAP-expressing cells in the spinal cord have distinct functional enrichments and may be regulated by cluster-specific transcription factors. Further research may help to develop new treatments for SCI that target specific subpopulations of glial progenitor cells.