Single-Cell Census of Human Tooth Development Enables Generation of Human Enamel
This week we profile a recent publication in Developmental Cell from the lab of Dr. Hannele Ruohola-Baker (pictured) at UW’s Department of Biochemistry
Can you provide a brief overview of your lab’s current research focus?
Our lab translates discoveries about the fundamentals of human development into new ideas for improving health outcomes for people everywhere. We study the molecules, cellular properties, and signaling pathways that drive (or disrupt) stem cell differentiation both in normal development and in cases of real-world challenges related to cancer, heart disease, muscle disorders, infertility, COVID-19, dental health, and more. Through ongoing collaborations with the UW Institute for Protein Design, our goal is to contribute to tools with the potential to regulate genes and treat diseases with unprecedented precision.
What is the significance of the findings in this publication?
The tissues that form our teeth do not regenerate like skin or hair. Enamel may be the hardest material in the human body, but once it’s gone, it’s gone. Without it, the dentin that makes up most of our teeth and pulp containing the nerves and blood vessels are more vulnerable to damage, increasing the likelihood of cavities, tooth loss, and other complications.
We are hopeful that regenerative medicine approaches may give dentists around the world new ways to help suffering patients. One key is figuring out how to restart the production of ameloblasts – the cells that are responsible for enamel formation early in life, but no longer present once a tooth erupts from the gums. Achieving that would require learning to harness the biological processes that naturally drive ameloblasts.
We, as a team from UW’s Institute for Stem Cell and Regenerative Medicine, have partnered with the School of Dentistry, the Institute for Protein Design, and the Brotman Baty Institute to map the signaling pathways that are necessary for ameloblast and dentin growth. It has also allowed us to develop a tooth organoid that can be used for disease modeling now while pointing to the future of dental care. Our research combines stem cell, designed protein, and single-cell sequencing technologies, and we’re excited to share it in our recent publication in Developmental Cell.
In short, there are three key advancements from our paper: the first single cell sequencing atlas of the developing tooth, the first induced pluripotent stem cell-derived tooth organoid, and the first designed protein application in regenerative dentistry. The ability to generate tooth organoids that secrete the essential ingredients of enamel (ameloblastin, amelogenin and enamelin) may usher in a “Century of Living Fillings” in which stem cell-derived tissues could be used to repair cavities and other oral health challenges dentists see in the clinic.
What are the next steps for this research?
We now hope to refine the process to make an enamel comparable in durability to that found in natural teeth and develop ways to use this enamel to restore damaged teeth. One approach would be to create enamel in the laboratory that could then be used to fill cavities and other defects.
This research is funded by: the NIH, the National Heart, Lung and Blood Institute Progenitor Cell Biology Consortium, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, UW Medicine Institute of Stem Cell and Regenerative Medicine Fellowships, the Dr. Douglass L. Morell Research Fund, and the Hahn Family. Work conducted in the Institute for Stem Cell and Regenerative Medicine’s Genomics Core was supported by a gift from the John H. Tietze Foundation