Nagata Mizuki, Chu Angel Ka Yan, Ono Noriaki, Welch Joshua D, Ono Wanida
Department of Orthodontics, University of Texas Health Science Center at Houston School of Dentistry, Houston, TX, United States.
Department of Computational Medicine and Bioinformatics, Department of Computer Science and Engineering, University of Michigan, Ann Arbor, MI, United States.
Front Dent Med. 2021 Aug;2. doi: 10.3389/fdmed.2021.679937. Epub 2021 Aug 12.
The periodontium is essential for supporting the functionality of the tooth, composed of diversity of mineralized and non-mineralized tissues such as the cementum, the periodontal ligament (PDL) and the alveolar bone. The periodontium is developmentally derived from the dental follicle (DF), a fibrous tissue surrounding the developing tooth bud. We previously showed through lineage-tracing experiments that DF contains mesenchymal progenitor cells expressing parathyroid hormone-related protein (PTHrP), which give rise to cells forming the periodontal attachment apparatus in a manner regulated by autocrine signaling through the PTH/PTHrP receptor. However, the developmental relationships between PTHrP DF cells and diverse cell populations constituting the periodontium remain undefined. Here, we performed single-cell RNA-sequencing (scRNA-seq) analyses of cells in the periodontium by integrating the two datasets, i.e. PTHrP-mCherry DF cells at P6 and 2.3kb Col1a1 promoter-driven GFP periodontal cells at P25 that include descendants of PTHrP DF cells, cementoblasts, osteoblasts and periodontal ligament cells. This integrative scRNA-seq analysis revealed heterogeneity of cells of the periodontium and their cell type-specific markers, as well as their relationships with DF cells. Most importantly, our analysis identified a cementoblast-specific metagene that discriminate cementoblasts from alveolar bone osteoblasts, including (encoding PTHrP) and . RNA velocity analysis indicated that cementoblasts were directly derived from PTHrP DF cells in the early developmental stage and did not interconvert with other cell types. Further, CellPhoneDB cell-cell communication analysis indicated that PTHrP derived from cementoblasts acts on diversity of cells in the periodontium in an autocrine and paracrine manner. Collectively, our findings provide insights into the lineage hierarchy and intercellular interactions of cells in the periodontium at a single-cell level, aiding to understand cellular and molecular basis of periodontal tissue formation.
牙周组织对于支持牙齿的功能至关重要，它由多种矿化和非矿化组织组成，如牙骨质、牙周韧带（PDL）和牙槽骨。牙周组织在发育上源自牙囊（DF），这是一种围绕发育中的牙胚的纤维组织。我们之前通过谱系追踪实验表明，DF包含表达甲状旁腺激素相关蛋白（PTHrP）的间充质祖细胞，这些细胞以通过PTH/PTHrP受体的自分泌信号调节的方式产生形成牙周附着装置的细胞。然而，PTHrP DF细胞与构成牙周组织的不同细胞群体之间的发育关系仍不明确。在这里，我们通过整合两个数据集，即P6时的PTHrP-mCherry DF细胞和P25时的2.3kb Col1a1启动子驱动的GFP牙周细胞，对牙周组织中的细胞进行了单细胞RNA测序（scRNA-seq）分析，其中包括PTHrP DF细胞的后代、成牙骨质细胞、成骨细胞和牙周韧带细胞。这种整合的scRNA-seq分析揭示了牙周组织细胞的异质性及其细胞类型特异性标志物，以及它们与DF细胞的关系。最重要的是，我们的分析确定了一种成牙骨质细胞特异性元基因，可将成牙骨质细胞与牙槽骨成骨细胞区分开来，包括（编码PTHrP）和。RNA速度分析表明，成牙骨质细胞在发育早期直接源自PTHrP DF细胞，并且不与其他细胞类型相互转化。此外，CellPhoneDB细胞间通讯分析表明，源自成牙骨质细胞的PTHrP以自分泌和旁分泌方式作用于牙周组织中的多种细胞。总的来说，我们的研究结果在单细胞水平上为牙周组织细胞的谱系层次和细胞间相互作用提供了见解，有助于理解牙周组织形成的细胞和分子基础。
