Yao Jinzhong, Deng Huan, Wang Peng, Li Bo, Qin Zaisheng
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.
Department of Anesthesiology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518033, China.
Open Med (Wars). 2025 Apr 15;20(1):20251178. doi: 10.1515/med-2025-1178. eCollection 2025.
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.
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.
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.
In summary, Spp1, C1qbp, and Myc are LRGs that are predominantly expressed in microglia and play regulatory roles in various stages of IS.
本研究旨在阐明缺血性中风（IS）后小胶质细胞中乳酸相关基因（LRGs）的动态变化及其与免疫细胞的关联。
我们对批量测序（GSE30655和GSE35338）和单细胞RNA测序数据（GSE174574）进行差异表达分析，以鉴定差异表达基因。将这些基因与来自MSigDB的乳酸基因进行交叉分析，以确定中风后的LRGs。我们使用t-SNE来可视化LRG在不同细胞类型中的分布，并选择小胶质细胞进行细胞间通讯、伪时间和功能富集分析。这些发现与GSE225948单细胞RNA测序数据集相结合，以研究IS慢性期的LRG趋势。最后，使用CIBERSORT来探索IS后免疫细胞浸润变化以及LRG与免疫细胞的关联。
鉴定出9个LRGs，包括Spp1、Per2、Col4a1、Sfxn4、C1qbp、Myc、Apln、Cdo1和Cav1，其中Spp1、C1qbp和Myc在小胶质细胞中高表达。C1qbp和Myc在急性期至关重要，而Spp1影响IS的急性期和慢性期。小胶质细胞亚群分析揭示了四个亚群（MG0-MG3）。免疫细胞浸润分析表明这些基因与免疫细胞之间存在显著关联。
总之，Spp1、C1qbp和Myc是主要在小胶质细胞中表达的LRGs，在IS的各个阶段发挥调节作用。
