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

Alghadeer, Ammar; Patni, Anjali P.; Ehnes, Devon; Zhao, Yan Ting; Li, Zicong; Phal, Ashish; Vincent, Thomas L.; Lim, Yong Bin; O’Day, Diana R.; Spurrell, Cailyn H.; Gogate, Aishwarya A.; Zhang, Hai; Devi, Arikketh; Wang, Yuliang; Doherty, Dan; Glass, Ian A.; Shendure, Jay; Freedman, Benjamin; Baker, David; Regier, Mary C.; Mathieu, Julie; Ruohola‐Baker, Hannele

doi:10.1016/j.devcel.2023.07.013

Cited by 14 publications

(14 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alghadeer et al. performed scRNA-seq on human tooth germs at their different developmental stages (9–22 gestational weeks) as well as developing salivary glands and jaws [ 18 ]. In the tooth sample data, major cell clusters included the dental mesenchyme, dental epithelium, odontoblasts, and ameloblasts.…”

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

“…Cellular trajectory proposed by Alghadeer et al. [ 18 ] is illustrated in the upper panel and summarized in the lower panel. The oral epithelium gives rise to the dental epithelium, which differentiates into the OEE (1) and enamel knot/SR lineages (2).…”

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

“…The enamel knot is known to be an essential signaling center during tooth development, especially for determining crown shape [ 2 ]. The authors found that the enamel knot cluster appeared twice at 9–11 (an early cap stage) and 14–16 (an early bell stage) gestational weeks [ 18 ], potentially reflecting formation of the primary and secondary enamel knot, respectively, in the scRNA-seq data. In addition, gene ontology (GO) analysis revealed that the clusters were associated with morphogenesis- and appendage development-related genes [ 18 ], which supports the developmental significance of the enamel knot.…”

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

“…The transcriptome-based clustering identified the SI and SR, each with inner and outer populations; spatial mapping also demonstrated that the inner SI was the cell layer closer to the ameloblast lineage, whereas the outer SI was present as parallel cells adjacent to the inner SI [ 18 ]. The inner SI was associated with Hh and Wnt signaling, and the outer SI with TGF-β signaling.…”

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

“…In the predicted trajectory, the OEE-derived cervical loop was a source of the ameloblast lineage; the authors also found a small LGR6 + population in the cervical loop [ 18 ], which was shown to contain Lgr5 + dental epithelial stem cells in mouse incisors [ 19 ]. These data support a role of the cervical loop in differentiation of the ameloblast lineage during crown expansion.…”

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

See 4 more Smart Citations

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling

Eldeeb,

Ikeda,

Hojo

et al. 2024

Regenerative Therapy

View full text Add to dashboard Cite

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

Section: Cellular Characterization Of the Dental Epithelium-ameloblas...mentioning

confidence: 99%

See 3 more Smart Citations

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling

Eldeeb,

Ikeda,

Hojo

et al. 2024

Regenerative Therapy

View full text Add to dashboard Cite

The temporal protein signature analyses of developing human deciduous molar tooth germ

Chen,

Li,

Zhang

et al. 2024

Proteomics

View full text Add to dashboard Cite

The tooth serves as an exemplary model for developmental studies, encompassing epithelial‐mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time‐dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap‐to‐early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co‐expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single‐cell RNA‐sequencing (scRNA‐seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

show abstract

From Pluripotent Stem Cells to Organoids and Bioprinting: Recent Advances in Dental Epithelium and Ameloblast Models to Study Tooth Biology and Regeneration

Hermans,

Hasevoets,

Vankelecom

et al. 2024

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Ameloblasts are the specialized dental epithelial cell type responsible for enamel formation. Following completion of enamel development in humans, ameloblasts are lost and biological repair or regeneration of enamel is not possible. In the past, in vitro models to study dental epithelium and ameloblast biology were limited to freshly isolated primary cells or immortalized cell lines, both with limited translational potential. In recent years, large strides have been made with the development of induced pluripotent stem cell and organoid models of this essential dental lineage – both enabling modeling of human dental epithelium. Upon induction with several different signaling factors (such as transforming growth factor and bone morphogenetic proteins) these models display elevated expression of ameloblast markers and enamel matrix proteins. The advent of 3D bioprinting, and its potential combination with these advanced cellular tools, is poised to revolutionize the field – and its potential for tissue engineering, regenerative and personalized medicine. As the advancements in these technologies are rapidly evolving, we evaluate the current state-of-the-art regarding in vitro cell culture models of dental epithelium and ameloblast lineage with a particular focus toward their applicability for translational tissue engineering and regenerative/personalized medicine. Graphical Abstract Future perspectives for in vitro modeling of dental epithelium and ameloblasts. Development of iPSC and organoid models that can reliably generate dental epithelium and ameloblast-like cells, together with advances in 3D bioprinting, provide promising tools for enamel research. Advanced models will provide new avenues for development of enamel repair/regeneration approaches, for testing of dental materials or drugs, studying host-pathogen and/or cell-cell interactions, in vitro modeling of enamel diseases (e.g. amelogenesis imperfecta) and developing novel insights in fundamental tooth biology (e.g. regulation of amelogenesis, lineage specification). Abbreviations: iPSC: induced pluripotent stem cells; TO: tooth organoids; DE: dental epithelium; AB: ameloblast.

show abstract

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

Cited by 14 publications

References 78 publications

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling

The temporal protein signature analyses of developing human deciduous molar tooth germ

From Pluripotent Stem Cells to Organoids and Bioprinting: Recent Advances in Dental Epithelium and Ameloblast Models to Study Tooth Biology and Regeneration

Contact Info

Product

Resources

About