Integrating Bulk RNA and Single-Cell Sequencing Data Reveals Genes Related to Energy Metabolism and Efferocytosis in...

Background/Objectives: Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals' health. The interplay between energy metabolism and apoptosis is critical, as the loss of viable cells in the intervertebral disc (IVD) can lead to a cascade of degenerative changes. Efferocytosis is a key biological process that maintains homeostasis by removing apoptotic cells, resolving inflammation, and promoting tissue repair. Therefore, enhancing mitochondrial energy metabolism and efferocytosis function in IVD cells holds great promise as a potential therapeutic approach for LDH. Methods: In this study, energy metabolism and efferocytosis-related differentially expressed genes (EMERDEGs) were identified from the transcriptomic datasets of LDH. Machine learning approaches were used to identify key genes. Functional enrichment analyses were performed to elucidate the biological roles of these genes. The functions of the hub genes were validated by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and Control groups. Additionally, we used single-cell RNA sequencing dataset to analyze cell-specific expression of the hub genes. Results: By using bioinformatics methods, we identified six EMERDEGs hub genes (IL6R, TNF, MAPK13, ELANE, PLAUR, ABCA1) and verified them using RT-qPCR. Functional enrichment analysis revealed that these genes were primarily associated with inflammatory response, chemokine production, and cellular energy metabolism. Further, we identified candidate drugs as potential treatments for LDH. Additionally, in immune infiltration analysis, the abundance of activated dendritic cells, neutrophils, and gamma delta T cells varied significantly between the LDH group and Control group. The scRNA-seq analysis showed that these hub genes were mainly expressed in chondrocyte-like cells. Conclusions: The identified EMERDEG hub genes and pathways offer novel insights into the molecular mechanisms underlying LDH and suggest potential therapeutic targets.