Integration of single cell analysis of dental mesenchyme and human disease database identifies the responsible gene of dentin disorders

Objectives

Dental anomalies are often associated with inherited diseases and are frequently seen in the field of pediatric dentistry. Dentin disorders are caused by genetic mutations of genes expressed in dental mesenchyme and these genetic mutations also cause skeletal dysplasia. However, only little genes are identified as the responsible gene of dentin disorders and therefore the genetic mechanism is poorly understood. Here, we identified the dental mesenchymal cell-specific genes using single-cell RNA-sequence (scRNA-seq) to clarify the pathogenesis of dentin disorders. Furthermore, we examined the association of inherited disease with dentin or skeletal abnormality using human disease database.

Materials and methods

scRNA-seq were performed using post-natal day (P) seven mice incisor. Total 6260 cells of scRNA-seq dataset was obtained. Top 20 differentially expressed genes (DEGs) in odontoblast cluster and dental pulp cluster were identified. Inherited diseases of DEGs and their Clinical Synopsis were examined using Online Mendelian Inheritance in Man (OMIM).

Results

The prevalence of inherited disease was 17/40 genes (42.5 %) and dental anomalies-associated inherited diseases were 12/35 diseases (34.3 %); 2.8 % in enamel abnormality, 14.3 % in dentin abnormality, and 17.1 % in other abnormality. The prevalence of dentin abnormality was 33.3 % in odontoblast and 7.7 % in dental pulp-associated diseases. The prevalence of skeletal abnormality in identified inherited diseases was 85.7 %.

Conclusion

The DEGs in dental mesenchymal cells were highly associated with dentin abnormality and skeletal abnormality. Identification of dental mesenchymal cell specific genes using scRNA-seq may uncover the novel genetic mechanism of dentin disorders.