衰弱与非衰弱高龄老人外周血单个核细胞单细胞转录组特征差异分析

The transcriptome characteristics of single cells in the peripheral blood mononuclear cells between frail and non-frail elderly

目的已有研究表明衰老和衰弱影响人体免疫细胞转录组异质性和变异性。本研究着重探寻不同衰弱状态下高龄老人外周血转录组特征差异。方法下载基因表达数据库(GEO)中的GSE157007数据集,分析衰弱与非衰弱高龄老人外周血单个核细胞分布、特征,对差异表达基因(DEGs)进行京都基因与基因组百科全书(KEGG)通路富集分析,并采用CellChat包分析细胞间的相互作用和通讯情况。结果与非衰弱组相比,衰弱组中T细胞、单核细胞总比例降低,自然杀伤(NK)细胞比例升高,B细胞比例相当。组间各细胞亚群DEGs存在差异,通路富集分析发现DEGs主要富集于抗原呈递、肿瘤坏死因子信号通路和趋化因子信号等通路。进一步细胞通讯分析显示衰弱组细胞间相互作用数目和强度均少于非衰弱组,组间细胞间相互作用的模式和信号通路不同。结论不同衰弱状态的高龄老人外周血单细胞转录组特征存在差异。

Objective Recent studies have found that aging and frailty affect transcriptome heterogeneity and variability.Based on the existing evidence,this study aims to explore the differences in the transcriptome characteristics of peripheral blood of older people under different frailty states.Methods The dataset(GSE157007)was downloaded from the Gene Expression Omnibus(GEO).The distribution and characteristics of cells and the differentially expressed genes between frail and non-frail elderly were analyzed.The differentially expressed genes were performed by Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The interaction and communication between cells were also studied by CellChat package.Results Compared with the non-frail group,the proportion of T cells and monocytes in the frail group was reduced,while the ratio of natural killer cells was increased.No significant difference was found in the cluster of B cells.And there were significant differences in gene expression among cell clusters.KEGG pathway analysis showed that differentially expressed genes were mainly enriched in antigen presentation,Tumor necrosis factor signaling pathway,chemokine signaling pathways.Further analysis of cell communication showed that the number and intensity of interactions between cells of the frail group were less than those in the non-frail group,and frailty states might affect the mode and signaling pathway of interactions between cells.Conclusion Significant differences were observed in the transcriptome characteristics of single cells in older people with different frailty states.