文献类型：期刊文献

中文题名：基于单细胞转录组测序数据识别糖尿病肾病发生发展的关键细胞

英文题名：Identification of Key Cells in the Development of Diabetic Nephropathy Basedon Single-cell Transcriptome Sequencing Data

作者：杨蕤[1,2];万生芳[1];张磊[1];李荣科[1];杨雅丽[1];王同亮[1,2];张亚男[1];魏昭辉[1];白晓丹[1];荀敏奇[1]

第一作者：杨蕤

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2023

卷号：36

期号：20

起止页码：1

中文期刊名：医学信息

外文期刊名：Journal of Medical Information

基金：国家自然科学基金项目(编号:82060914,81560718)。

语种：中文

中文关键词：糖尿病肾病;单细胞转录组测序;间质细胞;巨噬细胞

外文关键词：Diabetic kidney disease;Single-cell transcriptome sequencing;Stromal cell;Macrophagocyte

摘要：目的通过单细胞转录组学与大样本表型数据分析糖尿病肾病(DKD)患者肾组织中细胞数量变化以及肾小球组织中相关细胞表型变化,分析在DKD疾病发生发展中起关键性作用的细胞与重要生物学功能。方法通过GEO数据库选取单细胞数据集GSE131882,使用FindClusters功能对细胞进行聚类,并使用marker基因对得到的细胞群体进行细胞类型鉴定。选取GEO数据库中GSE96804作为表型数据,使用R4.2.0版本中Scissor包识别DKD发病正相关的细胞亚群,筛选关键细胞后绘制差异基因表达火山图,随后对DKD发生发展过程中关键细胞的基因表达进行GSEA富集,并将结果可视化后进行分析。结果结合单细胞类型鉴定与Scissor结果得出,DKD患者巨噬细胞和间充质细胞、肾β-闰细胞、肾毛细血管内皮细胞、成纤维细胞4种间质细胞Scissor+细胞比例明显高于Scissor-细胞,且细胞数量变化较大;关键细胞通过GSEA分析得出,差异基因主要富集在Toll样受体信号通路、氧化磷酸化信号通路、黏着斑信号通路、ECM受体相互作用信号通路等。结论肾小球中间充质细胞、肾β-闰细胞、肾毛细血管内皮细胞、成纤维细胞4种间质细胞以及巨噬细胞可能是导致DKD发生发展的关键原因,炎症、能量代谢等功能可能是影响DKD的重要功能。
Objective To analyze the changes of cell number in renal tissue and related cell phenotype in glomerular tissue of patients with diabetic kidney disease(DKD)by single cell transcriptomics and large sample phenotypic data,and to analyze the cells and important biological functions that play a key role in the occurrence and development of DKD disease.Methods The single-cell data set named GSE131882 was chosen from the GEO database,and the cells were then clustered using the FindClusters function.The resulting cell population's cell types were then determined using marker genes.The phenotypic data named GSE96804 was chosen from the GEO database,and the Scissor program in the R4.2.0 version was used to identify cell subsets that were positively connected to the pathogenesis of DKD.After screening the key cells,the volcano map of differential gene expression was plotted,then the gene expression of key cells in the development of DKD was enriched by GSEA,and the results were visualized and analyzed.Results When single cell type identification was combined with Scissor results,it was discovered that the proportion of Scissor+cells,which included macrophagocyte,mesenchymal cells,kidney beta-intercalated cells,kidney capillary endothelial cells,and fibroblasts,was significantly higher in DKD patients than that of Scissor-cells.Key cell GSEA analysis revealed that the differential genes were predominantly enriched in the signaling pathways for Toll-like receptors,oxidative phosphorylation,focal adhesion,and ECM-receptor interaction,among other signaling pathways.Conclusion The primary causes of the occurrence and progression of DKD may be attributed to four different types of stromal cells in the glomerulus,including mesenchymal cells,kidney beta-intercalated cells,kidney capillary endothelial cells,fibroblasts,and macrophagocyte.Functions such as energy metabolism,inflammation,and others may have a significant impact on DKD.