Single-cell and Spatial Transcriptomic Profiling of Gingival Tissues in Aggressive and Chronic Periodontitis: Deciphering Cellular Heterogeneity and Inflammatory Microenvironment Features

Second Affiliated Hospital, School of Medicine, Zhejiang University9 enrolled

Overview

The goal of this observational study is to investigate cellular heterogeneity and inflammatory microenvironment features in gingival tissues from patients with aggressive periodontitis compared to chronic periodontitis and healthy controls, using single-cell and spatial transcriptomics combined with whole-genome sequencing. The main question(s) it aims to answer are: What are the differences in cellular composition, mesenchymal stem cell subpopulations, and gene expression profiles between aggressive periodontitis, chronic periodontitis, and healthy gingival tissues? Which key molecular markers, signaling pathways, and spatially resolved microenvironment patterns distinguish aggressive periodontitis from the more common chronic form? Are there disease-specific genetic variants associated with aggressive periodontitis identified through whole-genome sequencing of peripheral blood DNA? Participants (already scheduled for tooth extraction or periodontal surgery as part of routine clinical care) will undergo: Standard clinical periodontal examination and CBCT imaging Collection of a small gingival tissue sample (\~1×3×1 mm) during the planned extraction/surgery under local anesthesia Collection of 5 mL peripheral blood for DNA extraction No additional intervention, treatment, or follow-up visit is required beyond routine dental care. Last updated: December 23, 2025

Study Type

OBSERVATIONAL

Enrollment

Conditions

Periodontis Aggressive Periodontitis

Eligibility

Sex: ALLMin age: 20 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Aggressive Periodontitis Patients: 1. Aged 20-35 years 2. Radiographic evidence of at least 30% vertical bone loss at ≥2 tooth sites 3. Can be classified as Stage III/IV, Grade C periodontitis according to the 2018 new classification of periodontitis 4. With or without family history of periodontitis 5. No significant local contributing factors (e.g., calculus, occlusal trauma, etc.) Chronic Periodontitis Patients: 1. Aged 30-40 years 2. ≥3 sites with probing depth ≥5 mm 3. Can be classified as Stage I/II, Grade A/B periodontitis according to the 2018 new classification of periodontitis 4. No significant family history 5. Disease predominantly driven by local factors (dental plaque, calculus, etc.) Healthy Controls: 1. Aged 20-40 years 2. Radiographic examination shows no significant alveolar bone loss 3. Clinically cannot be diagnosed with gingivitis or periodontitis Exclusion Criteria: 1. Use of antibiotics within the past 3 months 2. Smoking \>10 cigarettes per day 3. Uncontrolled severe diabetes (HbA1c level ≥6.7%) 4. Planning pregnancy, currently pregnant, or breastfeeding 5. Alcohol or drug addiction 6. Long-term use of immunosuppressive agents 7. Infectious diseases such as hepatitis or AIDS/HIV 8. History of malignant tumor, radiotherapy, or chemotherapy within the past 5 years

Outcomes

Primary Outcomes

Landscape of Cellular Heterogeneity in Periodontal Tissues

Single-cell RNA sequencing (scRNA-seq) will be used to evaluate the cellular heterogeneity of gingival tissues from patients with aggressive periodontitis (AP group), chronic periodontitis (CP group), and healthy controls, with a particular focus on mesenchymal stem cells. This includes identification of cell subpopulations and quantification of these subpopulations based on gene expression profiles.

Time frame: 1 year

Identification of Key Molecular Markers and Signaling Pathways

To discover differentially expressed molecular markers and signaling pathways between the AP group, CP group, and healthy group. By integrating single-cell RNA sequencing and spatial transcriptomics data, the analysis will identify potential therapeutic targets.

Time frame: 1 year

Secondary Outcomes

Spatial Transcriptomic Expression Profiles

Evaluation of the spatial distribution patterns of gene expression in gingival tissues from the aggressive periodontitis (AP) group, chronic periodontitis (CP) group, and healthy controls, as well as treatment-induced spatial changes. Spatial transcriptomics technology will be used to map cell-cell interactions and differences in the microenvironment.

Time frame: 1 year

Genetic Variants Identified by Whole-Genome Sequencing

Through whole-genome resequencing (WGS) of peripheral blood DNA, identification of genetic susceptibility variants associated with aggressive periodontitis and chronic periodontitis, with a particular focus on variants related to familial aggregation, genetic predisposition, disease progression, and treatment response.

Time frame: 1 year

Single-cell and Spatial Transcriptomic Profiling of Gingival Tissues in Aggressive and Chronic Periodontitis: Deciphering Cellular Heterogeneity and Inflammatory Microenvironment Features

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts