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

Ammar Alghadeer; Sesha Hanson-Drury; Anjali P Patni; Devon D Ehnes; Yan Ting Zhao; Zicong Li; Ashish Phal; Thomas Vincent; Yen C Lim; Diana O'Day; Cailyn H Spurrell; Aishwarya A Gogate; Hai Zhang; Arikketh Devi; Yuliang Wang; Lea Starita; Dan Doherty; Ian A Glass; Jay Shendure; Benjamin S Freedman; David Baker; Mary C Regier; Julie Mathieu; Hannele Ruohola-Baker

doi:10.1016/j.devcel.2023.07.013

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

Dev Cell. 2023 Oct 23;58(20):2163-2180.e9. doi: 10.1016/j.devcel.2023.07.013. Epub 2023 Aug 14.

Authors

Ammar Alghadeer¹, Sesha Hanson-Drury², Anjali P Patni³, Devon D Ehnes⁴, Yan Ting Zhao², Zicong Li⁴, Ashish Phal⁵, Thomas Vincent⁶, Yen C Lim⁴, Diana O'Day⁷, Cailyn H Spurrell⁸, Aishwarya A Gogate⁹, Hai Zhang¹⁰, Arikketh Devi¹¹, Yuliang Wang¹², Lea Starita¹³, Dan Doherty¹⁴, Ian A Glass¹⁴, Jay Shendure¹⁵, Benjamin S Freedman¹⁶, David Baker¹⁷, Mary C Regier¹⁸, Julie Mathieu¹⁹, Hannele Ruohola-Baker²⁰

Affiliations

¹ 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.
² 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.
³ 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; Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Chennai 603203, India.
⁴ 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.
⁵ 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 Bioengineering, University of Washington, Seattle, WA 98195, USA.
⁶ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
⁷ Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
⁸ Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
⁹ Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Seattle Children's Research Institute, Seattle, WA 98195, USA.
¹⁰ Department of Restorative Dentistry, University of Washington, School of Dentistry, Seattle, WA 98195, USA.
¹¹ Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Chennai 603203, India.
¹² Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
¹³ Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
¹⁴ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98195, USA.
¹⁵ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
¹⁶ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle WA 98109.
¹⁷ 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; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
¹⁸ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
¹⁹ Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
²⁰ 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; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. Electronic address: hannele@uw.edu.

PMID: 37582367
PMCID: PMC10629594 (available on 2024-10-23)
DOI: 10.1016/j.devcel.2023.07.013

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.

Keywords: ameloblast; amelogenesis imperfecta; directed differentiation; hiPSC; odontoblast; organoids; pathway analysis; regenerative dentistry; sci-RNA-seq; tooth development.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Ameloblasts / metabolism
Amelogenesis / genetics
Dental Enamel*
Humans
Odontogenesis*
Tooth*

Abstract

Publication types

MeSH terms

Grants and funding