Epithelial Edar is Responsible for Dental Anomalies in HED
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE300760 | GEO | 2026/05/03
REPOSITORIES: GEO
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Project description:Dental epithelial stem cells give rise to all dental epithelial cell types, inner enamel epithelium, outer enamel epithelium, ameloblasts, stratum intermedium and stellate reticulum to form enamel. These all types of epithelial cells have distinct roles and are essential for enamel formation. These cell types are conventionally classified by their cell shape, however, the transcriptome and biological roles of each cell types are not fully understood. Here, we used single-cell RNA-sequencing to clarify the heterogeneity of dental epithelial cell types. Unbiased clustering of 6260 single-cells from post-natal day 7 mouse incisors are classified into 4 dental epithelial and 2 mesenchymal populations; 2 clusters of ameloblast, IEE/OEE and SI/SR clusters. Secretory-stage of ameloblasts were divided into Dspp+ or Ambn+ ameloblast. Pseudo-time analysis indicated that Dspp+ ameloblast differentiate into Ambn+ ameloblast. Further, Dspp and Ambn would be stage-specific markers of ameloblast. Gene Ontology (GO) analyses of each clusters indicate potent roles of cell types; OEE in regulation of tooth size and SR in transport of nutrition. Moreover, we identified novel dental epithelial cell marker genes, Pttg1, Atf3, Cldn10 and Krt15. These results provide a resource of transcriptome data in dental cells and contribute further molecular analyses of enamel formation.
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2023-04-19 | E-MTAB-12544 | biostudies-arrayexpress
Project description:Tooth enamel secreted by ameloblasts is the hardest material in the human body, acting as a shield protecting the teeth. However, 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.
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Project description:Little is known about the role of cell-cell adhesion in the development of mineralized tissues. Here we report that PERP, a tetraspan membrane protein essential for epithelial integrity, is a critical regulator of enamel formation. Perp is necessary for proper cell attachment and gene expression during tooth development, and its expression is controlled by P63, a master regulator of stratified epithelial development. During enamel formation, PERP is localized to the interface between the enamel-producing ameloblasts and the stratum intermedium (SI), a layer of cells subjacent to the ameloblasts. Perp-null mice display dramatic enamel defects, which are caused, in part, by the detachment of ameloblasts from the SI. Microarray analysis comparing gene expression in teeth of wild-type and Perp-null mice identified several differentially expressed genes during enamel formation. Analysis of these genes in ameloblast-derived LS8 cells upon knock down of PERP confirmed the role for PERP in the regulation of gene expression. Together, our data show that PERP is necessary for the integrity of the ameloblast-SI interface and that the lack of Perp causes downregulation of genes that are critical for proper enamel formation. Two-condition experiment, RNA isolated from WT vs. Perp-null lower 1st molars. Biological replicates: 3 control replicates, 3 mutant replicates.
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Project description:Nogo-A is a major player in the regulation of neural development and regeneration, and it is the target of several clinical trials. Despite its high clinical relevance, the functions of Nogo-A outside the central nervous system are mostly unknown. In this work, we investigated the role of Nogo-A in tooth development in mouse transgenic models. We observed that Nogo-A is expressed in ameloblasts, the cells responsible for the formation of enamel. We show that the deletion of Nogo-A in the dental epithelium leads to the formation of defective enamel. By RNA sequencing we showed that this phenotype is associated with the overexpression of clusters of genes involved in cell differentiation and production of enamel.
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Project description:Little is known about the role of cell-cell adhesion in the development of mineralized tissues. Here we report that PERP, a tetraspan membrane protein essential for epithelial integrity, is a critical regulator of enamel formation. Perp is necessary for proper cell attachment and gene expression during tooth development, and its expression is controlled by P63, a master regulator of stratified epithelial development. During enamel formation, PERP is localized to the interface between the enamel-producing ameloblasts and the stratum intermedium (SI), a layer of cells subjacent to the ameloblasts. Perp-null mice display dramatic enamel defects, which are caused, in part, by the detachment of ameloblasts from the SI. Microarray analysis comparing gene expression in teeth of wild-type and Perp-null mice identified several differentially expressed genes during enamel formation. Analysis of these genes in ameloblast-derived LS8 cells upon knock down of PERP confirmed the role for PERP in the regulation of gene expression. Together, our data show that PERP is necessary for the integrity of the ameloblast-SI interface and that the lack of Perp causes downregulation of genes that are critical for proper enamel formation.
2011-01-22 | GSE26796 | GEO
Project description:Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta. Identifying proteins critical in ameloblast development can provide insight into specific pathologies associated with enamel related disorders or more broadly, mechanisms of mineralization. Previous studies identified a role for MEMO1 in bone mineralization; however, whether MEMO1 functions in the generation of additional mineralized structures remains unknown. Here, we identify a critical role for MEMO1 in enamel mineralization. First, we identified that Memo1 is expressed in ameloblasts and that conditional deletion of Memo1 from ameloblasts results in enamel defects, characterized by a decline in mineral density and tooth integrity. Molecular profiling of ameloblasts and their progenitors in Memo1 oral epithelial mutants revealed a disruption to cytoskeletal associated genes and a reduction in late stage ameloblast markers, relative to controls. Histology revealed that the molecular defects correlated with a disruption of the apical Tome’s process and the basolateral interacting, papillary layer, in Memo1 mutant ameloblasts. Finally, deletion of Memo1 from an oral epithelial ameloblast cell line, followed by cellular and molecular analyses, revealed altered cytoskeletal networks, relative to control cells. Collectively, our findings integrate MEMO1 into an emerging network of molecules important for ameloblast development and provide both in vivo and in vitro systems to further interrogate the relationship of cytoskeletal and amelogenesis-related defects.
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Project description:The goal of the study was to characterize the whole genome transcriptome profiles of human ameloblasts and odontoblasts, evaluate molecular pathways and advance our knowledge of the human tooth development. We found that during primary tooth formation, odontoblasts expressed 14,802 genes, presecretory ameloblasts 15,179 genes and secretory ameloblasts 14,526 genes. Four human fetuses were obtained at ages 15-20 weeks gestation, immediately placed on ice and the tooth buds dissected from the jaws, placed in RNAlater and refrigerated at 4C for 1-4 weeks to allow decalcification by EDTA. The tissue was then frozen and stored at -80C. The tissue was sectioned at -35C at a thickness of 7 microns. These sections were used for laser capture microdissection (LCM) to isolate the human odontoblasts and ameloblasts in different stages of enamel formation, using static image settings. In total, 4 odontoblast, 4 pre-secretory ameloblast and 4 secretory ameloblast pooled samples were used for RNA extraction and microarray analysis.
2014-11-14 | E-GEOD-63289 | biostudies-arrayexpress
Project description:The tooth is a convenient experimental model for the study of the basic mechanisms of organ development, including differentiation, cellular interaction, morphogenesis, and production and mineralization of extracellular matrices. The rodent incisor teeth grow continuously and exhibit all stages of tooth development at any time. This characteristic makes them convenient models for the study of enamel formation, which occurs in several distinct stages along the tooth axis. The distribution and structure of mouse incisor enamel resemble that of the rat. The enamel covers only the labial aspect of the tooth, and can be divided into four layers: a thin inner prism-free layer, inner enamel with prism decussation, i.e. transverse rows of prisms with prisms inclined medially and laterally in alternate rows, outer enamel with parallel prisms inclined incisally and a thin superficial prism-free layer. Recently, we have described how this elaborate organization of the enamel is established in the initial enamel formed on the unerupted and unworn incisal tip of the incisors. The very first enamel formed, i.e. the most incisally situated enamel, is always prism-free, corresponding to the superficial layer in fully established enamel, although thicker. Going in apical direction, i.e. in the direction of initiation of new enamel formation, isolated prisms appear among the crystals continuous with the prism-free zone crystals. These initial prisms are in general inclined incisally, corresponding to the prisms in the outer enamel layer in the fully established enamel. Inner enamel with the characteristic decussation pattern is added somewhat further apically and increases in thickness with increasing enamel thickness. Based on the structure of the enamel that they produce, the ameloblasts producing the initial, thin, prism-free enamel at the incisal tip of the unworn mouse incisor are probably differently configured (e.g. lacking Tomes' processes), probably differently organized (e.g. not organized in transverse rows moving sideways in opposite directions), and probably have a shorter life-span than the more apically situated ameloblasts which produce thicker enamel with the full four-layered configuration of mouse incisor enamel. For this reason it would be of interest to compare the gene expression profile of the incisal tip segment where prism-free enamel is being formed with the profile of the immediately adjacent segment where enamel with all four layers is being formed. As long as the incisor is unworn enamel formation and gene expression in these segments will likely reflect mechanistic differences between these segments as regards enamel biosynthesis. MicroRNAs (miRNA) are a class of non-coding RNAs that regulate gene expression at a post-transcriptional level, and are considered as important regulatory molecules during foetal development. By binding to target mRNA, miRNA induce mRNA decay or translation repression. Recent bioinformatic predictions of miRNA targets in vertebrates indicate that hundreds of miRNAs are responsible for regulating the expression of up to 30% of the human protein-coding genes, and miRNAs have recently also been shown to regulate expression of hundreds of mRNAs in cultured cells. Recently, miRNA expression profiles of the developing murine molar tooth germ and submandibular salivary gland have been established. We here report expression profiling of miRNAs present in the two adjacent segments of the incisor tooth germ on which we also have carried out mRNA expression profiling. The results suggest that also miRNAs are abundantly, and differentially, expressed during development of the incisor tooth germ in mouse. By analogy with the mRNA data also miRNA expression is dynamic, with respect to both the two incisor segments investigated and to the developmental stage of the incisor.
2010-10-01 | E-MTAB-149 | biostudies-arrayexpress
Project description:Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. Because enamel is acellular and has limited capacity to heal, regenerative technologies are highly desirable, yet have remained largely out of reach. This is in part due to the challenges of synthesizing crystallites with similar properties and assembling them in a mechanically robust structure. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When implanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model for the development of the dental epithelium and enamel, and an important first step towards regrowth or replacement of enamel.
2023-11-18 | GSE220686 | GEO