Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons

Nature Communications, 2022 · DOI: 10.1038/s41467-022-33184-1 · Published: September 23, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following spinal cord injury, the tissue distal to the injury site contains cells that could potentially aid in recovery. The study uses single-nucleus RNA sequencing to analyze how different cell types in the lumbar spinal cord respond to a thoracic injury in mice. The research presents an atlas of the dynamic responses across various cell types in the spinal cord at different stages of injury: acute, subacute, and chronic. This atlas helps identify rare spinal neurons that exhibit a regenerative signature after injury. The study characterizes these cells anatomically and observes axonal sparing, outgrowth, and remodeling in the spinal cord and cerebellum. This suggests a spontaneous plasticity of spinocerebellar neurons, making them potential targets for therapy.

Study Duration

Acute to Chronic time points (1 day to 6 weeks post injury)

Participants

Mice (C57BL/6), both male and female, aged 12-30 weeks

Evidence Level

Not specified

Key Findings

1
Rare spinal neurons, particularly spinocerebellar projection neurons, express a signature of regeneration in response to spinal cord injury.
2
Spinocerebellar neurons exhibit axonal sparing, outgrowth, and remodeling in both the spinal cord and cerebellum after injury.
3
An atlas of cell-type specific responses in the lumbar spinal cord following SCI was created using single nucleus RNA Sequencing (snRNA-seq).

Research Summary

The study presents a single-cell atlas of the lumbar spinal cord after thoracic spinal cord injury in mice, detailing cell type-specific responses across acute, subacute, and chronic stages. The research identifies a pro-regenerative transcriptional signature in rare spinal neurons, particularly spinocerebellar neurons, and demonstrates their axonal sparing and outgrowth after injury. The findings highlight the spontaneous plasticity of spinocerebellar neurons and their potential as therapeutic targets for promoting recovery after spinal cord injury.

Practical Implications

Therapeutic Targeting

Spinocerebellar neurons, identified as displaying spontaneous plasticity, may be leveraged as therapeutic targets for promoting recovery after spinal cord injury.

Understanding Regeneration

The identified regeneration-associated genes (RAGs) expressed by spinocerebellar neurons provide insights into the molecular mechanisms underlying spontaneous axon outgrowth and remodeling.

Clinical Application

The detailed atlas of cell-type specific responses to spinal cord injury can serve as a valuable resource for developing targeted interventions to enhance recovery and tissue remodeling.

Study Limitations

1
The use of nuclei instead of whole cells for transcriptional profiling may result in fewer genes detected per cell/nucleus and may slightly bias the cellular composition.
2
The global overview of all cell types in the lumbar spinal cord should be followed up by future studies on specific cell types after spinal cord injury enabling deeper analysis of the molecular pathways and trauma responses of each cell type.
3
The atlas component of this work examines changes at the gene expression level and does not address post-transcriptional cellular mechanisms.

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