Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
J Dent Res. 2023 Jun;102(6):645-655. doi: 10.1177/00220345231159821. Epub 2023 May 6.
The metabolism and remodeling of alveolar bone are the most active among the whole skeletal system, which is related to the biological characteristics and heterogeneity of the bone mesenchymal stromal cells (MSCs). However, there is a lack of systematic description of the heterogeneity of MSC-derived osteoblastic lineage cells as well as their distinct osteogenic differentiation trajectory of alveolar bone. In this study, we constructed a single-cell atlas of the mouse alveolar bone cells through single-cell RNA sequencing (scRNA-seq). Remarkably, by comparing the cell compositions between the alveolar bone and long bone, we uncovered a previously undescribed cell population that exhibits a high expression of protocadherin (Fat4 cells) and is specifically enriched around alveolar bone marrow cavities. ScRNA-seq analysis indicated that Fat4 cells may initiate a distinct osteogenic differentiation trajectory in the alveolar bone. By isolating and cultivating Fat4 cells in vitro, we demonstrated that they possess colony-forming, osteogenic, and adipogenic capabilities. Moreover, FAT4 knockdown could significantly inhibit the osteogenic differentiation of alveolar bone MSCs. Furthermore, we revealed that the Fat4 cells exhibit a core transcriptional signature consisting of several key transcription factors, such as SOX6, which are involved in osteogenesis, and further demonstrated that SOX6 is required for the efficient osteogenic differentiation of the Fat4 cells. Collectively, our high-resolution single-cell atlas of the alveolar bone reveals a distinct osteogenic progenitor that may contribute to the unique physiological characteristics of alveolar bone.
肺泡骨的代谢和重塑是整个骨骼系统中最活跃的，这与骨间充质基质细胞（MSCs）的生物学特性和异质性有关。然而，对于 MSC 衍生的成骨谱系细胞的异质性及其独特的肺泡骨成骨分化轨迹，还缺乏系统的描述。在这项研究中，我们通过单细胞 RNA 测序（scRNA-seq）构建了小鼠肺泡骨细胞的单细胞图谱。值得注意的是，通过比较肺泡骨和长骨之间的细胞组成，我们揭示了一个以前未被描述的细胞群体，该群体高表达原钙黏蛋白（Fat4 细胞），并特异性富集在肺泡骨骨髓腔周围。scRNA-seq 分析表明，Fat4 细胞可能在肺泡骨中启动了一个独特的成骨分化轨迹。通过体外分离和培养 Fat4 细胞，我们证明它们具有集落形成、成骨和成脂能力。此外，FAT4 的敲低可显著抑制肺泡骨 MSC 的成骨分化。此外，我们揭示了 Fat4 细胞表现出一个由几个关键转录因子组成的核心转录特征，如参与成骨的 SOX6，进一步证明 SOX6 是 Fat4 细胞有效成骨分化所必需的。总之，我们对肺泡骨的高分辨率单细胞图谱揭示了一个独特的成骨祖细胞，它可能有助于肺泡骨的独特生理特征。
