单细胞转录组测序解析糖尿病肾病肾小管上皮细胞转分化过程中的关键基因调控网络  

Single-Cell RNA Sequencing Analysis of Key Gene Regulatory Networks during the Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells in Diabetic Nephropathy

作　　者：张白岩 Zhang Baiyan(Henan Xinxiang Medical College,Xinxiang 453003,China)

机构地区：[1]河南新乡医学院,河南新乡453003

出　　处：《新医学（新加坡）》2024年第1期51-58,共8页

摘　　要：糖尿病肾病是糖尿病常见且严重的微血管并发症,肾小管上皮细胞转分化在其病理进程中起核心作用。本研究旨在利用单细胞转录组测序技术解析糖尿病肾病肾小管上皮细胞转分化过程中的关键基因调控网络。共纳入30例糖尿病肾病患者及20例健康对照,采集肾脏组织样本进行单细胞转录组测序。经数据质控与分析,在细胞层面鉴定出肾小管上皮细胞的三个亚群(TEC1、TEC2、TEC3),各亚群具有独特基因表达特征。差异表达基因分析筛选出500个差异表达基因,功能分类显示涉及细胞间黏附、上皮-间质转化及细胞外基质代谢等相关基因变化显著。构建的关键基因调控网络确定了10个核心转录因子,如SNAI1、TWIST1等,它们与靶基因相互作用促进细胞转分化。本研究为深入理解糖尿病肾病发病机制提供了单细胞水平的证据,且为治疗靶点筛选及策略制定提供了理论依据,尽管存在样本量有限等局限性,但为后续多中心、多组学联合研究及药物研发等奠定了基础。Diabetic nephropathy is a common and severe microvascular complication of diabetes,and the epithelial-mesenchymal transition of renal tubular epithelial cells plays a central role in its pathological process.The aim of this study was to use single-cell RNA sequencing technology to analyze the key gene regulatory networks during the epithelial-mesenchymal transition of renal tubular epithelial cells in diabetic nephropathy.A total of 30 patients with diabetic nephropathy and 20 healthy controls were included,and kidney tissue samples were collected for single-cell RNA sequencing.Through data quality control and analysis,three subpopulations of renal tubular epithelial cells(TEC1,TEC2,TEC3)were identified at the cellular level,and each subpopulation had unique gene expression characteristics.Differential expression gene analysis screened out 500 differentially expressed genes,and functional classification showed significant changes in genes related to cell-cell adhesion,epithelial-mesenchymal transition,and extracellular matrix metabolism.The constructed key gene regulatory network identified 10 core transcription factors,such as SNAI1,TWIST1,etc.,which interact with target genes to promote cell transdifferentiation.This study provides evidence at the single-cell level for a deeper understanding of the pathogenesis of diabetic nephropathy and offers a theoretical basis for the screening of therapeutic targets and the formulation of treatment strategies.Although there are limitations such as a limited sample size,it lays the foundation for subsequent multicenter,multi-omics joint studies and drug development.

关 键 词：糖尿病肾病 单细胞转录组测序 肾小管上皮细胞 转分化 基因调控网络 

分 类 号：R73[医药卫生—肿瘤]