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首页|Human iPSC Derived Enamel Organoid Guided by Single-Cell Atlas of Human Tooth Development

Human iPSC Derived Enamel Organoid Guided by Single-Cell Atlas of Human Tooth Development

Human iPSC Derived Enamel Organoid Guided by Single-Cell Atlas of Human Tooth Development

来源:bioRxiv_logobioRxiv
英文摘要

Abstract Tooth enamel secreted by ameloblasts is the hardest material in the human body, acting as a shield protecting 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 sci-RNA-seq to establish a spatiotemporal single-cell atlas for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We reveal key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in a novel human ameloblast in vitro differentiation from iPSCs. We furthermore develop a mineralizing enamel organ-like 3D organoid system. These studies pave the way for future regenerative dentistry and therapies toward genetic diseases affecting enamel formation.

Spurrell CH、Ehnes D、Hanson-Drury S、Patni AP、Gogate AA、Phal A、Zhang H、Glass I、Shendure J、Mathieu J、Doherty D、Devi A、Ruohola-Baker H、Alghadeer A、Zhao YT、Regier MC、Starita L、Baker D、Wang Y、O?ˉDay D

Brotman Baty Institute for Precision MedicineDepartment of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of MedicineDepartment of Oral Health Sciences, University of Washington, School of Dentistry||Department of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of MedicineDepartment of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and TechnologyBrotman Baty Institute for Precision Medicine||Seattle Children?ˉs Research InstituteDepartment of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Department of Bioengineering, University of WashingtonDepartment of Restorative Dentistry, University of Washington, School of DentistryInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Department of Pediatrics, University of Washington||Center for Integrative Brain Research, Seattle Children?ˉs Research InstituteInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Brotman Baty Institute for Precision MedicineInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Department of Comparative Medicine, University of Washington, School of MedicineInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Department of Pediatrics, University of Washington||Center for Integrative Brain Research, Seattle Children?ˉs Research InstituteCancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and TechnologyDepartment of Biomedical Dental Sciences, Imam Abdulrahman bin Faisal University, College of Dentistry||Department of Oral Health Sciences, University of Washington, School of Dentistry||Department of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Seattle Children?ˉs Research InstituteDepartment of Biomedical Dental Sciences, Imam Abdulrahman bin Faisal University, College of Dentistry||Department of Oral Health Sciences, University of Washington, School of Dentistry||Department of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of MedicineDepartment of Oral Health Sciences, University of Washington, School of Dentistry||Department of Biochemistry, University of Washington, School of Medicine||Institute for Stem Cell and Regenerative Medicine, University of Washington, School of MedicineInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of MedicineBrotman Baty Institute for Precision MedicineDepartment of Biochemistry, University of Washington, School of MedicineInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine||Paul G. Allen School of Computer Science and Engineering, University of WashingtonDepartment of Pediatrics, University of Washington||Brotman Baty Institute for Precision Medicine

10.1101/2022.08.09.503399

口腔科学基础医学生物科学研究方法、生物科学研究技术

Spurrell CH,Ehnes D,Hanson-Drury S,Patni AP,Gogate AA,Phal A,Zhang H,Glass I,Shendure J,Mathieu J,Doherty D,Devi A,Ruohola-Baker H,Alghadeer A,Zhao YT,Regier MC,Starita L,Baker D,Wang Y,O?ˉDay D.Human iPSC Derived Enamel Organoid Guided by Single-Cell Atlas of Human Tooth Development[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2022.08.09.503399.点此复制

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