GEO公共数据库中4例多指畸形患者细胞间质和上皮细胞的单细胞转录组分析  

Single-cell transcriptome analysis of mesenchymal and epithelial cells from four patients with polydactyly in the GEO public database

作　　者：傅东升[1,2] 艾克热木江•木合热木 Fu Dongsheng;Aikeremujiang•Muheremu(Department of Orthopedics,Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830001,Xinjiang Uygur Autonomous Region,China;Key Laboratory of Orthopedic Regenerative Medicine,Xinjiang Medical University,Urumqi 830001,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学第六附属医院骨科,新疆维吾尔自治区乌鲁木齐市830001 [2]新疆医科大学骨科再生医学重点实验室,新疆维吾尔自治区乌鲁木齐市830001

出　　处：《中国组织工程研究》2025年第20期4379-4388,共10页Chinese Journal of Tissue Engineering Research

基　　金：新疆维吾尔自治区自然科学基金 (2020D01C196),项目负责人:傅东升。

摘　　要：背景:多指畸形患者中参与Heghog信号通路的一些转录因子发生异常表达,这些转录因子调控大量靶基因的表达,从而影响细胞的功能。目的:通过单细胞转录组分析多指畸形患者的转录组特征。方法:从GEO公共数据库中下载4例多指畸形患者细胞间质和上皮细胞的单细胞转录组数据,将成纤维细胞和角质细胞划分为细胞亚群,并分析不同亚群的转录因子,构建转录因子及其靶基因的调控网络,分析调控因子的功能。结果与结论:对单细胞的转录谱数据进行分析发现,与多指畸形中细胞功能高度相关的调控因子有HOXD13、MSX2、LHX2、EMX2、LEF1、CREB3L2以及LHX2等HOX家族成员和GLI2转录因子。成纤维细胞中的HOXD13、MSX2和LHX2在多指畸形过程中发挥作用,而HES2和GLIS1在角质细胞的形成和发育过程中起重要作用。结果表明:HOXD13、MSX2和LHX2等转录因子的高表达可能与多指畸形的发育密切相关。通过靶向特定的转录因子或调节其活性,可能为纠正或预防多指畸形提供潜在的治疗策略。BACKGROUND:Aberrant expression of some transcription factors involved in the Heghog signaling pathway occurs in patients with polydactyly,and these transcription factors regulate the expression of massive target genes,thereby affecting cellular function.OBJECTIVE:To analyze the transcriptome characterization of patients with polydactyly by single-cell transcriptome analysis.METHODS:The single-cell transcriptome data of mesenchymal and epithelial cells of four patients with polydactyly were downloaded from the GEO public database.Fibroblasts and keratinocytes were categorized into cell subsets,and the transcription factors within each subset were examined.A regulatory network of these transcription factors and their target genes was developed,and the functions of these regulatory factors were analyzed.RESULTS AND CONCLUSION:The transcriptional profiling data of individual cells indicated that the regulatory factors strongly linked to cell functionality in polydactyly include the transcription factors HOXD13,MSX2,LHX2,EMX2,LEF1,CREB3L2,and LHX2 of the HOX family and GLI2 transcription factors.In fibroblasts,HOXD13,MSX2,and LHX2 are involved in polydactyly,whereas HES2 and GLIS1 are crucial for the formation and development of keratinocytes.To conclude,the elevated expression of transcription factors including HOXD13,MSX2,and LHX2 is potentially closely associated with the development of polydactyly.Potential therapeutic strategies that may be offered to correct or prevent polydactyly by targeting specific transcription factors or modulating their activity.

关 键 词：多指畸形 转录因子 生物信息学 单细胞转录组分析 微环境 Heghog信号通路 大数据分析 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R658.2