首页|期刊导航|辐射研究与辐射工艺学报|伽马射线照射对小鼠肠道干细胞及分化细胞关键基因的影响及鉴定

伽马射线照射对小鼠肠道干细胞及分化细胞关键基因的影响及鉴定OA

Effects and identification of gamma irradiation on key genes of intestinal stem cells and differentiated cells in mice

中文摘要英文摘要

研究γ射线对小鼠肠道中肠道干细胞及其分化细胞表达谱的影响,筛选关键基因.利用Seurat包对单细胞数据(GSE165318)进行聚类分析和差异表达分析,通过TCseq包进行时间序列的表达趋势分析,对肠道干细胞及分化细胞的差异上调基因和特定趋势基因簇取交集得到关键基因.分别采用clusterProfiler软件包和STRING数据库对关键基因进行基因本体(Gene ontology,GO)富集分析和蛋白质-蛋白质相互作用网络分析(Protein-protein interaction,PPI).利用60Co γ射线腹部照射12 Gy构建放射性肠损伤小鼠模型,在辐照后第0天、3天、7天收集小肠组织.对关键基因进行实时荧光定量PCR(Real-time quantitative PCR,RT-qPCR)验证.结果鉴定出12种肠道细胞类型,在肠道干细胞及其分化细胞共5种细胞中挖掘到关键基因Mmp8.Mmp家族中有15个成员表达量在照后第3天达到峰值,且在不同细胞类型中的表达具有异质性.PPI网络分析结果显示,Mmp蛋白家族中Mmp3、Mmp7、Mmp8、Mmp9、Mmp11处于调节网络的枢纽位置.Mmp8、Mmp9、Mmp13、Mmp19和Mmp25的差异表达在RT-qPCR中得到验证.结论是Mmp家族在伽马射线引起的肠道损伤和修复过程中扮演重要角色,其中Mmp8、Mmp9、Mmp13、Mmp19和Mmp25等关键基因可能作为肠道辐射损伤潜在的治疗靶点.

This study aims to investigate the effect of gamma irradiation on the expression profile of intestinal stem cells(ISCs)and their differentiated cells in the intestine of mice,as well as to screen for key genes.The Seurat package was used to perform cluster analysis and differential expression analysis on a single-cell sequencing dataset(GSE165318)to identify differentially expressed genes in each cell type.The TCseq package analyzed the expression trend over time.Key genes were identified by intersecting up-regulated genes with specific trend gene clusters across the five cell types.The clusterProfiler package and STRING database were used for gene ontology(GO)enrichment analysis and PPI network analysis of key genes.A mouse model of radiation-induced intestinal injury(RIII)was established via abdominal irradiation with 12 Gy of 60Co γ-rays.Intestinal tissues were collected at 0,3,and 7 days post-irradiation in control and treatment groups.Key genes were verified using real-time quantitative PCR(RT-qPCR).The results showed that twelve intestinal cell types were identified,and the key gene Mmp8 was found in ISCs and their differentiated cells.Additionally,the expression of 15 Mmp family members peaked on the 3rd day after irradiation,with heterogeneous expression across different cell types.PPI network analysis revealed that Mmp3,Mmp7,Mmp8,Mmp9,and Mmp11 are central in the regulatory network.The differential expression of Mmp8,Mmp9,Mmp13,Mmp19,and Mmp25 was validated by RT-qPCR.The Mmp family plays an important role in the process of intestinal injury caused by gamma rays and its repair,and Mmp8,Mmp9,Mmp13,Mmp19 and Mmp25 may be potential therapeutic targets for intestinal radiation injury.

张浩然;刘俊;张中伟;薛伟;王蜜蜜;刘青杰

中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088中国疾病预防控制中心辐射防护与核安全医学所辐射防护与核应急中国疾病预防控制中心重点实验室 北京 100088

生物科学

γ射线单细胞测序放射性肠损伤基质金属蛋白酶

Gamma raysSingle-cell sequencingRadiation-induced intestinal injuryMatrix metalloproteinase

《辐射研究与辐射工艺学报》 2026 (3)

37-46,10

国家自然科学基金项目(82173463)资助 Supported by National Natural Science Foundation of China(82173463)

10.11889/j.1000-3436.2025-0111

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