中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (19): 4949-4964.doi: 10.12307/2026.224

• 干细胞培养与分化 stem cell culture and differentiation • 上一篇    下一篇

单细胞测序数据识别牙周炎患者的差异表达基因和免疫细胞亚型

仇雪笛1，2，郭  超1，何佳玥1，2，周  政1   

  1. 1石河子大学第一附属医院口腔科，新疆维吾尔自治区石河子市   832000；2石河子大学医学院，新疆维吾尔自治区石河子市   832000
  • 收稿日期:2025-08-01 接受日期:2025-11-09 出版日期:2026-07-08 发布日期:2026-02-14
  • 通讯作者: 周政，主任医师，教授，硕士生导师，石河子大学第一附属医院口腔科，新疆维吾尔自治区石河子市 832000
  • 作者简介:仇雪笛，女，1992年生，汉族，2025年石河子大学毕业，硕士，主要从事口腔修复种植及牙周病方面的研究。
  • 基金资助:
    兵团科技计划资助基金(2023ZD062)，项目负责人：周政；石河子大学第一附属医院院级科技计划资助基金(ZP2024004)，项目负责人：仇雪笛

Single-cell sequencing data identifies differentially expressed genes and immune cell subtypes in periodontitis patients

Qiu Xuedi1, 2, Guo Chao1, He Jiayue1, 2, Zhou Zheng1   

  1. 1Department of Stomatology, The First Affiliated Hospital of Shihezi University, Shihezi 832000, Xinjiang Uyghur Autonomous Region, China; 2Medical College of Shihezi University, Shihezi 832000, Xinjiang Uyghur Autonomous Region, China
  • Received:2025-08-01 Accepted:2025-11-09 Online:2026-07-08 Published:2026-02-14
  • Contact: Zhou Zheng, Chief physician, Professor, Master’s supervisor, Department of Stomatology, The First Affiliated Hospital of Shihezi University, Shihezi 832000, Xinjiang Uyghur Autonomous Region, China
  • About author:Qiu Xuedi, MS, Department of Stomatology, The First Affiliated Hospital of Shihezi University, Shihezi 832000, Xinjiang Uyghur Autonomous Region, China; Medical College of Shihezi University, Shihezi 832000, Xinjiang Uyghur Autonomous Region, China
  • Supported by:
    Xinjiang Production and Construction Corps Science and Technology Program, No. 2023ZD062 (to ZZ); Hospital-level Science and Technology Program of The First Affiliated Hospital of Shihezi University, No. ZP2024004 (to QXD)

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摘要：

文题释义：

单细胞测序：通过检测细胞的异质性，为健康与病变组织中的细胞和分子特征提供全面而客观的表征。
孟德尔随机化：是一种以遗传变异为工具变量，专注于因果关系的探索，尤其适用于通过遗传变异的“自然随机分配”来研究因果效应，排除混杂因素对结果的影响，加强了因果推断证据强度的研究方法。

摘要
背景：牙周炎是一种慢性炎症性疾病，既往研究多聚焦于特定免疫细胞或细胞因子，因此，对于系统深入阐明牙周炎的免疫机制、发现新的干预靶点具有重要意义。
目的：分析牙周炎相关的免疫细胞亚群表达谱及与其有因果关系的关键差异表达基因，探索牙周炎与免疫细胞动力学的可能分子作用机制及关键基因。
方法：牙周炎的单细胞RNA测序数据来自GEO数据库以解析免疫细胞亚群异质性并识别差异表达基因。通过表达数量性状位点(eQTL)数据进行孟德尔随机化分析以推断免疫细胞基因表达与牙周炎风险之间的因果关系，对筛选出的因果关联基因进行通路富集及免疫浸润分析以揭示差异表达基因及免疫细胞与牙周炎发生发展的关联，CellChat轨迹分析探索细胞间通讯。为验证关键发现，收集20例石河子大学第一附属医院口腔科确诊牙周炎患者的牙龈组织(牙周炎组)及20例来自正畸拔牙或阻生牙拔除患者的健康牙龈组织样本(对照组)，采用RT-qPCR及免疫组化检测关键基因的表达。
结果与结论：综合分析确定了牙周炎中23个免疫细胞簇及3个与牙周炎风险存在显著因果的关键基因(膜联蛋白A1、溶质载体家族11成员1和波形蛋白)。通路富集分析揭示了它们参与了关键的免疫调节机制。免疫亚型受体配体及关键细胞亚型轨迹等进一步分析表征揭示了膜联蛋白A1、溶质载体家族11成员1和波形蛋白在疾病进展中的不同作用。与健康对照组比较，牙周炎组织中膜联蛋白A1、溶质载体家族11成员1和波形蛋白 mRNA表达水平上调(P < 0.05)。此研究揭示了牙周炎中免疫细胞亚群的关键作用，并验证出与牙周炎有因果关系的关键基因(膜联蛋白A1、溶质载体家族11成员1、波形蛋白)。

关键词: 免疫细胞, 单细胞测序, 孟德尔随机化, 牙周炎, 免疫浸润, 膜联蛋白A1(ANXA1), 溶质载体家族11成员1(SLC11A1), 波形蛋白(VIM)

Abstract: BACKGROUND: Periodontitis is a highly prevalent chronic inflammatory disease. Previous research has predominantly focused on specific immune cells or cytokines. Consequently, systematically elucidating its immune mechanisms and discovering novel therapeutic targets hold significant implications. 
OBJECTIVE: To analyze the expression profiles of periodontitis-associated immune cell subpopulations and identify key differentially expressed genes with a causal relationship to the disease, thereby exploring potential molecular mechanisms and key genes involved in periodontitis and immune cell dynamics. 
METHODS: Single-cell RNA sequencing data from the GEO database were used to analyze immune cell subset heterogeneity and identify differentially expressed genes. Mendelian randomization analysis was performed using expression quantitative trait loci data to infer causal relationships between immune cell gene expression and periodontitis risk. Pathway enrichment and immune infiltration analyses were performed on the identified causal genes to reveal the associations between differentially expressed genes and immune cells with the development and progression of periodontitis. CellChat trajectory analysis was used to explore intercellular communication. To validate key findings, gingival tissue samples were collected from 20 patients with periodontitis diagnosed by the Department of Stomatology at The First Affiliated Hospital of Shihezi University (periodontitis group) and 20 healthy gingival tissue samples from patients undergoing orthodontic or impacted tooth extraction (control group). RT-qPCR and immunohistochemistry were used to examine the expression of key genes.
RESULTS AND CONCLUSION: Comprehensive analysis identified 23 immune cell clusters in periodontitis and three key genes (annexin A1, solute carrier family 11 member 1, and vimentin) that were significantly causally associated with periodontitis risk. Pathway enrichment analysis revealed their involvement in key immune regulatory mechanisms. Further analysis and characterization of immune subtype receptor ligands and key cell subtype trajectories revealed distinct roles for annexin A1, solute carrier family 11 member 1, and vimentin in disease progression. Annexin A1, solute carrier family 11 member 1, and vimentin mRNA expression levels were upregulated in periodontitis tissues compared with healthy controls (P < 0.05). This study reveals the key role of immune cell subsets in periodontitis and validates key genes (annexin A1, solute carrier family 11 member 1, and vimentin) with a causal relationship with periodontitis.

Key words: immune cell, single-cell RNA sequencing, Mendelian randomization, periodontitis, immune infiltration, annexin A1 (ANXA1), solute carrier family 11 member 1 (SLC11A1), vimentin (VIM)

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