ScRNA analysis and ferroptosis‑related ceRNA regulatory network investigation in microglia cells at different time points after spinal cord injury

Journal of Orthopaedic Surgery and Research, 2023 · DOI: https://doi.org/10.1186/s13018-023-04195-5 · Published: September 13, 2023

Spinal Cord Injury Genetics

Simple Explanation

This study investigates the role of microglia, key immune cells in the central nervous system, at different times after spinal cord injury (SCI). It uses single-cell RNA sequencing data from mouse spinal cords at 3 and 14 days post-injury to identify inflammatory biomarkers associated with microglia. The research also explores ferroptosis, a form of cell death, and how it relates to inflammation in the CNS after SCI. By examining gene expression in microglia, the study aims to find key genes involved in the immune inflammatory process following SCI. The findings predict key genes, such as Stmn1 and Fgfbr1, involved in the immune inflammatory response associated with microglia at different time points after spinal cord injury at the single-cell level and may provide a molecular basis for better treatment of SCI.

Study Duration

3- and 14-days

Participants

ambidextrous C57BL/6 J mice with spinal cord injury

Evidence Level

Not specified

Key Findings

1
Microglia are associated with immune system regulation at different time points after SCI and can modulate cytokine production.
2
Stmn1 and Fgfbr1 were identified as key genes differentially expressed in microglia during 3- and 14-days after spinal cord injury and associated with iron death, respectively.
3
The expression of Stmn1 was strongly correlated with the infiltration ratio of activated CD4 T cells, while less Tgfbr1 were closely related to the infiltration ratio of Central memory CD4 T cells.

Research Summary

This research investigates the role of microglia and ferroptosis in spinal cord injury (SCI) using single-cell RNA sequencing data from mice at 3 and 14 days post-injury. The study identifies key genes associated with microglia and their involvement in the immune inflammatory response. Functional enrichment analysis confirmed that microglia are associated with immune system regulation and cytokine production at different time points after SCI. Stmn1 and Fgfbr1 were identified as differentially expressed genes in microglia, linked to iron death. The study proposes that the Stmn1-associated ceRNA regulatory network with Tgfbr1 might be a potential RNA regulatory mechanism affecting the outcome after SCI. These findings provide new insights into ferroptosis-related inflammatory response induced by different time points after SCI.

Practical Implications

Targeted Therapies

Stmn1 and Tgfbr1, identified as potential biomarkers, could be targeted for therapeutic interventions to modulate microglial inflammatory responses after SCI.

Drug Development

The study identifies potential drug molecules, such as POTASSIUM NITRATE and sertraline for Stmn1, and diazepam for Tgfbr1, that could be further investigated for their therapeutic effects on SCI.

RNA Regulatory Mechanisms

The proposed Stmn1-associated ceRNA regulatory network suggests a potential RNA regulatory mechanism that could be further explored to understand and influence outcomes after SCI.

Study Limitations

1
The study is based on data from mouse models, which may not fully represent the complexities of human SCI.
2
The mechanisms of how ferroptosis could alter the pathophysiological process after SCI require further investigation.
3
Further research is needed to validate the therapeutic potential of the identified drug molecules and RNA regulatory mechanisms.

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