Single-cell RNA sequencing provides new insights into the interaction between astrocytes and neurons after spinal cord injury in mice

Abstract

Background: Spinal cord injury (SCI) is a devastating neurological disease in which astrocytes play a central role. Understanding the relationship between different subtypes of astrocytes and neuron subtypes during the progression of SCI is critical to understanding the disease. Methods and results: In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptome data of acute, subacute and intermediate stages of SCI in mice as well as normal tissues. Different subtypes of astrocytes and neuronal cells were identified and their dynamic changes and functionalities during the development of SCI. An intriguing discovery was the identification of a specific subtype of astrocytes characterized by unique expression of Gap43, Vim, Aldoc, and Mt1. This subtype of cells shows similarities in gene expression with neurons and potentially transitioned into neurons during the course of SCI. Furthermore, we have uncovered the important role of the glycolytic pathway in this cellular transformation process. Furthermore, through cellular interaction analysis, we validated pathways (mdk-ptprz1,ptn-ptprz1,ptn-sdc3) associated with the potential conversion of these specific cell subsets into neurons. Finally, these cells were observed by fluorescence microscopy and critical gene expressions were validated by Western blot. Conclusions: The results of this study not only deepen our understanding of the mechanisms underlying SCI, but also provide new insights and opportunities for the development of novel therapeutic strategies and interventions.

Keywords

• Spinal cord injury
• Astrocytes
• scRNA-seq
• Glycolysis
• Cell reprogramming