Dynamic activation of lytic cell death-related programs identifies CD14 as a candidate hub gene associated with secondary injury after spinal cord injury - Summary - MDSpire
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Dynamic activation of lytic cell death-related programs identifies CD14 as a candidate hub gene associated with secondary injury after spinal cord injury
To identify key regulatory nodes and hub genes associated with lytic cell death-related programs during the progression of secondary spinal cord injury (SCI).
Approach:
Data Analysis: Public transcriptomic datasets were analyzed using single-sample gene set enrichment analysis (ssGSEA) to assess transcriptional activities related to pyroptosis, necroptosis, and ferroptosis.
Model Integration: Differential expression analysis, weighted gene co-expression network analysis, functional enrichment, and multiple machine learning models were combined to identify candidate hub genes.
Validation: Key findings were validated using an external human SCI-related cohort, RT-qPCR, immunofluorescence in a rat SCI model, and published single-cell RNA-seq data.
Key Findings:
Transcriptional activities related to pyroptosis, necroptosis, and ferroptosis increased after SCI, starting in the acute phase and persisting over time.
Lytic cell death-associated genes were primarily involved in inflammatory responses, immune regulation, and myeloid activation.
CD14 was identified as the most robust candidate hub gene associated with lytic cell death indices.
Interpretation:
Limitations:
Current findings are primarily associative.
Further functional studies are needed to determine if CD14 directly modulates lytic cell death-related pathways.
Conclusion:
CD14 is a candidate hub gene associated with myeloid inflammatory activation and lytic cell death-related signatures following SCI.
