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Adult Dental Epithelial Stem Cell-Derived Organoids Deposit Hydroxylapatite Biomineral

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE220686 | GEO | 2023/11/18

REPOSITORIES: GEO

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Single-cell RNA-sequencing from mouse incisor reveals dental epithelial cell-type specific genes

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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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Transcriptional profiling of wild-type vs Perp-null mice during tooth development

2011-01-22 | GSE26796 | GEO

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