Single-cell sequencing reveals the temporal expression characteristics of key molecules related to tooth agenesis and dental hard tissues in mouse molars
10.3760/cma.j.cn112144-20250605-00206
- VernacularTitle:单细胞测序解析先天缺牙及牙体硬组织相关分子在小鼠磨牙的时序表达特征
- Author:
Wei GUO
1
;
Xiangpu WANG
1
;
Tongyu SU
1
;
Siqi WEI
1
;
Xiaoyun PAN
1
;
Xiaohong DUAN
1
Author Information
1. 空军军医大学口腔医院 口腔生物医学教研室/口腔罕见病与遗传病门诊 口颌系统重建与再生全国重点实验室 国家口腔疾病临床医学研究中心 陕西省口腔医学重点实验室 空军军医大学口腔医院口腔生物学教研室,西安 710032
- Publication Type:Journal Article
- Keywords:
Tooth agenesis;
Tooth development;
Single-cell RNA sequencing;
Bioinformatics analysis
- From:
Chinese Journal of Stomatology
2025;60(9):987-996
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To utilize single-cell RNA sequencing (scRNA-seq) to untangle the temporal expression profiles of molecules associated with congenital tooth agenesis and dental hard tissue formation during mouse molar development, and to construct a comprehensive cell atlas spanning the entire developmental period from E13.5 to P7.5, thereby providing new insights into the molecular mechanisms underlying abnormal tooth development.Methods:scRNA-seq data of murine mandibular molar tooth germs at five developmental stages (E13.5, E14.5, E16.5, P3.5, P7.5) were obtained from the GEO database (accession: GSE189381). The Seurat pipeline was employed for quality control, data normalization, dimensionality reduction, and Harmony-based batch effect correction. Cellular subpopulations were identified through uniform manifold approximation and projection dimensionality reduction, while developmental trajectories were reconstructed using Monocle for pseudotime analysis.Results:scRNA-seq analysis profiling identified 27 distinct cellular clusters, which were annotated into twelve major cell types including epithelial cells, mesenchymal cells, and endothelial cells. Msx1 exhibited a bimodal expression pattern. Pax9 reached its peak at E14.5 and then gradually decreased. Eda had a low expression level with a diffuse distribution. In contrast, Amelx and Enam were barely expressed during the embryonic stage and were activated at P3.5. Dspp was ectopically highly expressed in epithelial cells from P3.5 to P7.5, while Dmp1 was specifically upregulated in mesenchymal cells at P7.5.Conclusions:The temporal expression patterns of key regulatory genes for tooth agenesis (Msx1, Pax9, Eda), ameloblast differentiation (Amelx, Enam), and odontoblast development (Dspp, Dmp1) during mouse molar development. These findings provide a theoretical foundation and potential therapeutic targets for deciphering the molecular mechanisms underlying tooth agenesis and other developmental dental anomalies, paving the way for targeted clinical interventions.