Single-cell census of human tooth development enables generation of human enamel.

Dev Cell

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

Published: October 2023


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Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629594PMC
http://dx.doi.org/10.1016/j.devcel.2023.07.013DOI Listing

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