Combination of single-cell and bulk RNA seq reveals the immune inﬁltration landscape and targeted therapeutic drugs in spinal cord injury

Frontiers in Immunology, 2023 · DOI: 10.3389/fimmu.2023.1068359 · Published: January 19, 2023

Spinal Cord Injury Immunology Bioinformatics

Simple Explanation

Spinal cord injury (SCI) can lead to an imbalanced inflammatory environment that hinders neural regeneration. This study aimed to identify immune genes and potential therapeutic drugs for SCI. Researchers used bulk RNA sequencing and single-cell RNA sequencing to analyze gene expression in mice after SCI, focusing on macrophages and microglia. The study identified specific immune genes (B2m, Itgb5, and Vav1) and showed that a drug, decitabine, could potentially promote spinal cord regeneration by influencing the behavior of macrophages and microglia.

Study Duration

Not specified

Participants

27 adult female C57BL/6 mice

Evidence Level

Original Research

Key Findings

1
B2m, Itgb5, and Vav1 were identified as key immune genes in macrophages/microglia during the subacute phase of SCI.
2
Decitabine treatment in mice decreased pro-inflammatory factors (TNF-a, IL-1b) and increased anti-inflammatory factors (IL-4, IL-10) at 2 weeks post-SCI.
3
Decitabine treatment improved neurological function score and electromyography in SCI mice at 6 weeks post-SCI.

Research Summary

This study combined bulk RNA-seq and scRNA-seq data to investigate the immune landscape in the subacute phase of spinal cord injury (SCI). The research identified key immune hub genes (B2m, Itgb5, Vav1) in macrophages/microglia and demonstrated that decitabine may promote nerve regeneration by modulating the polarization state of these cells. In vivo experiments showed that decitabine treatment improved neurological function and shifted macrophages/microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype.

Practical Implications

Therapeutic Targets

B2m, Itgb5, and Vav1 in macrophages/microglia may be key therapeutic targets to promote nerve regeneration in subacute SCI.

Drug Repurposing

Low-dose decitabine may be a potential therapeutic agent to promote spinal cord regeneration by regulating the polarization state of macrophages/microglia.

Immune Modulation

Regulating the dual role of the immune microenvironment is a potential strategy in managing neuroinflammation during SCI.

Study Limitations

1
Batch effects in Bulk RNA-seq analyses should be addressed, despite preprocessing with the “sva” package.
2
The injection dose and safety of decitabine need further evaluation in in vivo and in vitro experiments.
3
The possibility that decitabine may bind to genes other than the hub gene in macrophages/microglia for pharmacological effects.

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