Single-cell census of human tooth development enables generation of human enamel.
ameloblast
amelogenesis imperfecta
directed differentiation
hiPSC
odontoblast
organoids
pathway analysis
regenerative dentistry
sci-RNA-seq
tooth development
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
09
08
2022
revised:
05
05
2023
accepted:
19
07
2023
pmc-release:
23
10
2024
medline:
27
10
2023
pubmed:
16
8
2023
entrez:
15
8
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37582367
pii: S1534-5807(23)00360-X
doi: 10.1016/j.devcel.2023.07.013
pmc: PMC10629594
mid: NIHMS1937148
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2163-2180.e9Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE033016
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL099997
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM097372
Pays : United States
Organisme : NICHD NIH HHS
ID : R24 HD000836
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM081619
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL099993
Pays : United States
Organisme : NIDCR NIH HHS
ID : T90 DE021984
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083867
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.A., S.H.-D., Y.T.Z., D.D.E., Y.W., A.P.P., H.Z., J.M., D.B., and H.R.-B. are co-inventors on a patent application entitled “Human IPSC Derived Ameloblasts and Uses Thereof” (PCT/US2022/053517 filed 12/20/2022 and published 7/6/2023).
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