Single-cell transcriptomic outlook of human dental pulp in health and disease. Single-cell transcriptomic outlook of human dental pulp in health and disease

We present a collection of single-cell transcriptomic profiles of 6,810 pulpal cells isolated from a sound human maxillary third molars and carious teeth at different stages. We showed that the presence of deep, but not enamel caries, altered the immune cell compositions of the dental pulp. Differential expression analysis further revealed that the pro-inflammatory, anti-inflammatory and mineralization-related genes were upregulated in immune and stromal cells in deep dental caries. Cell-cell interaction prediction showed potential interactions between immune and stromal cells during homeostasis, and enhanced interactions between different cell types with macrophage during deep dental caries. Taken together, our study serves as a comprehensive survey of human pulpal cell heterogeneity, as well as provides novel molecular insights into dental pulps in health and disease. Overall design: The single-cell transcriptomic profiles from cells residing in dental pulp from a sound tooth, enamel caries and deep dental caries were compared. Cell type frequency and differential gene expression were analyzed. Cell-cell interactions were predicted from the expression level of ligands and receptors.

本研究构建了一套包含6810个牙髓细胞的单细胞转录组谱（single-cell transcriptomic profiles）数据集，这些细胞分离自健康人类上颌第三磨牙以及不同病程阶段的龋病（dental caries）患牙。研究表明，深龋（deep dental caries）而非釉质龋（enamel caries）的存在会改变牙髓的免疫细胞组成。差异表达分析（differential expression analysis）进一步显示，在深龋患牙的免疫细胞与基质细胞（stromal cells）中，促炎、抗炎及矿化相关基因均呈现上调表达。细胞间相互作用（cell-cell interaction）预测分析显示，在生理稳态（homeostasis）下免疫细胞与基质细胞间存在潜在相互作用；而在深龋状态下，不同细胞类型与巨噬细胞（macrophage）间的相互作用显著增强。综上，本研究全面解析了人类牙髓细胞的异质性（cell heterogeneity），并为健康与疾病状态下的牙髓组织提供了全新的分子层面认知。实验设计概述：本研究对比了健康人类上颌第三磨牙、釉质龋患牙及深龋患牙牙髓组织中细胞的单细胞转录组谱，分析了细胞类型频率与差异基因表达情况，并基于配体（ligand）与受体（receptor）的表达水平预测了细胞间相互作用。