Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke.

Objectives: This study aims to elucidate the dynamic changes in lactate-related genes (LRGs) in microglia following ischemic stroke (IS) and their associations with immune cells.

Methods: We performed differential expression analysis on bulk-sequencing (GSE30655 and GSE35338) and scRNA-seq data (GSE174574) to identify differentially expressed genes. These genes were intersected with lactate genes from MSigDB to identify post-stroke LRGs. We used t-SNE to visualize LRG distribution across cell types and selected microglia for cell-cell communication, pseudo time, and functional enrichment analyses. These findings were integrated with the GSE225948 scRNA-seq dataset to examine LRG trends in the chronic phase of IS. Finally, CIBERSORT was used to explore immune cell infiltration changes and LRG-immune cell associations post-IS.

Results: Nine LRGs were identified, including Spp1, Per2, Col4a1, Sfxn4, C1qbp, Myc, Apln, Cdo1, and Cav1, with Spp1, C1qbp, and Myc highly expressed in microglia. C1qbp and Myc are crucial in the acute phase, while Spp1 impacts both acute and chronic phases of IS. Microglia subcluster analysis revealed four subclusters (MG0-MG3). Immune cell infiltration analysis showed significant associations between these genes and immune cells.

Conclusion: In summary, Spp1, C1qbp, and Myc are LRGs that are predominantly expressed in microglia and play regulatory roles in various stages of IS.