Ph.D. Graduate Student Institute for Stem Cell & Regenerative Medicine at the University of Washington Seattle, Washington, United States
Abstract: Enamel, the hardest material in the human body is required to protect our living organ, tooth. However, over 90% of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel producing cells, ameloblasts. IPSC derived Ameloblasts (iAM) have promise in future regenerative dentistry however, today it is not known why iAM maturation requires intimate contact with the dentin producing cell type, odontoblast. Here we reveal that the critical signaling ligand emanating from odontoblasts for ameloblast maturation is Delta. We further developed a computer designed soluble Notch activator that can mature iAM organoids in a precedented manner, without interactions with odontoblast layer. This novel maturation procedure allows us to analyze the detailed requirement of Dlx3 function in ameloblasts, independent of its known function in odontoblasts. We show Dlx3 is required cell autonomously in Ameloblasts for Enamel and MMP20 expression.
