单细胞组学揭示免疫补体系统抑制作为牙周炎与阿尔茨海默病的共同病理机制
Single-cell Genomics Revealed Immunocomplement System Suppression as a Shared Pathogenic Cause of Periodontitis and Alzheimer's Disease
孙天萌 1孙泽文 1赵天元 1徐梦钰 1孙宏晨 1安政雯1
作者信息
- 1. 吉林大学白求恩口腔医学院,长春 130021
- 折叠
摘要
目的 牙周炎和阿尔茨海默病(AD)作为老年人常见病,发病率随年龄增长而增高.为了探究两种疾病之间是否存在共同致病因素,从而为 AD 的早期诊断提供理论依据,本研究利用单细胞转录组数据和 Bulk RNA-seq 测序数据解析牙周炎与 AD 之间致病风险的相关性.方法 从基因表达数据集(GEO)数据库下载牙周炎(GSE164241)和 AD(GSE157827)单细胞数据,包括 3 例患者样本与 3 例对照.对单细胞数据进行质控、数据整合、降维聚类、细胞类型注释及差异表达基因鉴定.比较两种疾病组间差异表达基因,获取共有的差异表达基因.随后对共有差异表达基因进行富集分析,并针对基因所编码蛋白构建蛋白质-蛋白质相互作用(PPI)网络以了解蛋白之间的相互作用关系.从 GEO 数据库下载牙周炎(GSE16134)与 AD(GSE63060)的 Bulk RNA-seq 芯片测序表达矩阵与样本信息,验证单细胞数据中 PPI 的核心基因表达量,评估基因与疾病的相关性.结果 通过对比牙周炎和 AD 的样本数据分析,发现牙周炎与AD 中共有的免疫细胞为CD163+髓系细胞群,其中牙周炎来源的髓系细胞,疾病组/对照组发现1934 个下调的差异表达基因,AD 来源的髓系细胞,疾病组/对照组发现 232 个下调的差异表达基因,两者取交集后得到49 个共有的下调差异表达基因,对其进行富集分析,主要富集于髓系细胞和补体相关反应等.进一步分析表明补体通路中的 STAB1 基因表达与牙周炎和 AD 呈显著负相关(P<0.05).结论 髓系细胞是牙周炎和 AD共有的免疫细胞,其中补体通路中 STAB1 基因是两种疾病发生过程中共同下调的免疫相关基因,并且与疾病的发生呈显著负相关,提示牙周炎患者中 STAB1 基因表达的检测可作为 AD 早期诊断和治疗的潜在靶点.
Abstract
Objective Periodontitis and Alzheimer's disease are prevalent among the elderly,with an incidence that increa-ses with age.To investigate the potential common pathogenic factors between the two diseases and provide a theoretical basis for the early diagnosis of Alzheimer's disease,the study analyzed the pathogenic risk correlation between periodontitis and Alzheimer's disease using single-cell transcriptomics data and Bulk RNA-seq sequencing data.Methods Single-cell data for PD(GSE164241)and AD(GSE157827)were downloaded from the Gene Expression Omnibus(GEO)database,including samples from 3 patients and 3 controls for each condition.The single-cell data were subjected to quality control,data integration,dimensionality reduction clustering,cell type annotation,and differential gene expression identification.Shared differentially expressed genes between the two diseases were i-dentified by comparing the gene expression profiles.Enrichment analysis of these shared genes was conducted,followed by the con-struction of a protein-protein interaction(PPI)network to understand the interactions between proteins.Bulk RNA-seq microarray ex-pression matrices and sample information for PD(GSE16134)and AD(GSE63060)were downloaded from the GEO database to vali-date the expression levels of core genes in the PPI network from the single-cell data and to assess the correlation between genes and dis-eases.Results Comparative analysis of sample data from periodontitis and Alzheimer's disease revealed CD163+myeloid cells as a common immune cell type in both conditions.In periodontitis-derived myeloid cells,1934 downregulated differentially expressed genes were found in the disease group compared to the control group,while in Alzheimer's disease-derived myeloid cells,232 downregulated genes were identified,with an intersection of 49 shared downregulated genes.Enrichment analysis of these genes primarily highlighted myeloid cell and complement system-related responses.Further analysis showed that the expression of STAB1 gene in the complement system was significantly negatively correlated with both periodontitis and Alzheimer's disease.Conclusion Myeloid cells are a com-mon immune cell type in both periodontitis and Alzheimer's disease.STAB1 acts as a downstream target of complement pathway closely related to both diseases and shows a significant negative correlation with disease onset.This suggests that the detection of STAB1 gene expression levels in periodontitis patients could serve as potential targets for the early diagnosis and treatment of Alzheimer's disease.
关键词
牙周炎/阿尔茨海默病/免疫反应/髓系细胞/补体Key words
Periodontitis/Alzheimer's disease/Immune response/Myeloid cells/Complement引用本文复制引用
基金项目
科技部"十四五"国家重点研发计划重点专项(2022YFC2504200)
国家自然科学基金面上项目(82270960)
吉林省财政厅科技项目(JCSZ2021893-35)
出版年
2024
国家科技期刊平台
NSTL
万方数据