Single-cell RNA-sequence of dental epithelium reveals responsible genes of dental anomalies in human

Dental anomalies show various symptoms and some of them are accompanied with inherited diseases. However, only a few of responsible genes of dental anomalies are identified. In this study, we aimed to establish a novel strategy for identification of responsible genes of dental anomalies using integration of single-cell RNA-sequence (scRNA-seq) and Online Mendelian Inheritance in Man (OMIM). Single cells were isolated from mandibular incisor of post-natal day (P) seven mice and scRNA-seq were performed. Top 20 differentially expressed genes between clusters were identified and used for further analyses. Inherited diseases of differentially expressed genes and their Clinical Synopsis were examined using OMIM. The prevalence of inherited disease was 43/80 genes (53.8%) and inherited diseases which associate with dental anomalies were 34/96 diseases (35.4%); 14.6% in enamel abnormality, 4.1% in dentin abnormality, and 16.7% in other abnormality. The prevalence of enamel abnormality was the highest in ameloblast, while that of other abnormality was high in non-ameloblast cell types. Chromosomal mapping of differentially expressed genes indicated that chromosome 4 has “hotspots” of dental anomalies-associated genes. The differentially expressed genes in dental epithelial cells were responsible for inherited disease which shows dental anomalies. The strategy employed in this study will contribute to identify the responsible gene for dental anomalies.