A single cell atlas of human teeth (Periodontium scRNA-seq)

Teeth exert fundamental functions related to mastication and speech. Despite their big biomedical interest, an overall picture of their cellular and molecular composition is still lacking. We here mapped the transcriptional landscape of the various stem cell populations and their microenvironments in human teeth at single-cell resolution. Our analysis identified significant cellular heterogeneity between the various dental tissues. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar in vivo, and that their distinctive behavior was due to substantial differences between their microenvironments. Furthermore, we showed that the evolutionarily conserved Notch signaling pathway is important for the interactions between dental stem cells and the diverse cell types composing their niches. Our findings reveal that the microenvironmental specificity is responsible for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards dental cell-based therapeutic approaches.牙齿在咀嚼与言语等生理功能中发挥核心作用。尽管牙齿受到生物医学领域的广泛关注，但目前仍缺乏对其细胞与分子组成的整体认知。本研究以单细胞分辨率绘制了人类牙齿各类干细胞群及其微环境的转录组图谱。分析发现，不同牙齿组织间存在显著的细胞异质性。出乎意料的是，各类干细胞群在体内的分子特征高度相似，其行为差异实则源于各自微环境的显著区别。此外，本研究证实，进化保守的Notch信号通路（Notch signaling pathway）在牙齿干细胞与其干细胞龛的各类组成细胞的相互作用中发挥关键作用。本研究结果表明，微环境特异性是导致不同牙齿区域内干细胞功能差异的主要原因，同时为基于细胞的牙齿治疗手段开辟了全新的研究视角。