Department of Biomedical Dental Sciences, Imam Abdulrahman bin Faisal University, College of Dentistry, Dammam 31441, Saudi Arabia; Department of Oral Health Sciences University of Washington, School of Dentistry, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Department of Oral Health Sciences University of Washington, School of Dentistry, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Dev Cell. 2023 Oct 23;58(20):2163-2180.e9. doi: 10.1016/j.devcel.2023.07.013. Epub 2023 Aug 14.
Tooth enamel secreted by ameloblasts (AMs) is the hardest material in the human body, acting as a shield to protect the teeth. However, the enamel is gradually damaged or partially lost in over 90% of adults and cannot be regenerated due to a lack of ameloblasts in erupted teeth. Here, we use single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) to establish a spatiotemporal single-cell census for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We identify key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in human ameloblast in vitro differentiation from induced pluripotent stem cells (iPSCs). We furthermore develop a disease model of amelogenesis imperfecta in a three-dimensional (3D) organoid system and show AM maturation to mineralized structure in vivo. These studies pave the way for future regenerative dentistry.
成釉细胞分泌的牙釉质是人体中最坚硬的物质，起到保护牙齿的作用。然而，由于萌出牙齿中缺乏成釉细胞，超过 90%的成年人的牙釉质会逐渐受损或部分丧失，且无法再生。在这里，我们使用单细胞组合索引 RNA 测序（sci-RNA-seq）技术，对人类牙齿的发育进行了时空单细胞普查，并确定了调控人类成釉细胞分化过程的调控机制。我们鉴定了在胎儿发育过程中成釉细胞和支持细胞之间涉及的关键信号通路，并在体外诱导多能干细胞（iPSCs）分化的人类成釉细胞中重现了这些发现。我们还在三维（3D）类器官系统中建立了釉质发育不全的疾病模型，并在体内显示了 AM 向矿化结构的成熟。这些研究为未来的再生牙科铺平了道路。
