Human iPSC Derived Enamel Organoid Guided by Single Cell Atlas of Human Tooth Development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA766055 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16053908.fastq.gz | Fastqsanger.gz | |||
| SRR16053909.fastq.gz | Fastqsanger.gz | |||
| SRR16053910.fastq.gz | Fastqsanger.gz | |||
| SRR16053911.fastq.gz | Fastqsanger.gz | |||
| SRR16053912.fastq.gz | Fastqsanger.gz |
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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.
2023-01-11 | GSE184749 | GEO
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:Biological sex determination of human remains by means of a minimally destructive surface acid etch of tooth enamel and subsequent identification of sex chromosome linked isoforms of Amelogenin– an enamel-forming protein - by nano-liquid chromatography mass spectrometry(nanoLC-MS).
2017-12-12 | PXD007856 | Pride
Project description:Throughout the various stages of tooth development, reciprocal epithelial-mesenchymal interactions are the driving force, for instance crucially involved in the differentiation of mature enamel-forming ameloblasts and dentin-producing odontoblasts. Here we established mouse tooth ‘assembloids’, comprised of tooth organoid-derived dental epithelial cells (from mouse molars and incisors) cultured together with molar dental pulp stem cells (DPSCs), to mimic these developmental interactions. Assembloids from both tooth types were grown both in basal- and differentiation-inducing conditions. Single cell transcriptomics analysis was applied to in detail characterize and validate the newly developed mouse tooth assembloid model and evaluate the induced differentiation processes.
2023-04-19 | E-MTAB-12544 | biostudies-arrayexpress
Project description:Sex of individuals, estimated on human remains, is important information in anthropological, archaeological and forensic researches. In forensic anthropology, this is one of the key points for identifying a person. In archeology and paleoanthropology, information about sex is important for reconstructing the social and biological structure of a group, lifestyle, and for modeling demographic and growth processes in the past. Sex estimation of adult individuals is possible according to morphological criteria when metric and descriptive features are used. In case of poor preservation of the adult skeletons, as well as on children's remains, sex estimation by morphological criteria has some limitations. Therefore regular attempts are made to attract alternative methods for sexing human remains. As one of such methods a liquid chromatography-mass spectrometry analysis of tooth enamel peptides can be used. The result of this analysis is the identification of certain fragments of amelogenins - the main structural proteins of the organic matrix of tooth enamel, which make up more than 90% of its protein content. Amelogenin genes are located on both the X- and Y-chromosomes and the products of these genes have structural differences that allow them to be differentiated from each other. In the process of maturation of tooth enamel, its protein matrix undergoes proteolytic degradation, as a result enamel already contains proteins in the form of their peptide fragments. Reliable and reproducible detection of unique peptide fragments of amelogenins encoded on the X- and Y-chromosomes in human enamel will make it possible to estimate sex of human remains. The work presents a peptidomic analysis of tooth enamel using chromatography-mass spectrometry. Experiments were carried out on a series of teeth of various archaeological data, tafonomic condition of crown and different biological generations of teeth (deciduous and permanent ones).
2020-06-24 | PXD017965 | Pride
Project description:In a systemic effort to survive environmental stress, organ systems fluctuate and adapt to overcome external pressures. The evolutionary drive back towards homeostasis, makes it difficult to determine if an organism experienced a toxic exposure to stress, especially in early prenatal and neonatal periods of development. Previous studies indicate that primary human teeth may provide historical records of experiences related to stressors during that early time window. To assess the molecular effects of early life adversity on enamel formation, we used a limited bedding and nesting (LBN) mouse model of early life adversity (ELA), to assess changes in enamel organ gene expression and enamel mineralization. Enamel of postnatal day 12 (P12) weight-matched ELA mice was more mineralized as compared control enamel. RNAseq showed 724 genes significantly upregulated in ELA enamel organs as compared to controls, and 574 significantly downregulated genes (DESeq2 p-value <= 0.05). Transcripts expressing the enamel matrix proteins amelogenin (Amelx) and enamelin (Enam) were among the top 4 most differentially expressed genes. The most significantly enriched GO and Reactome pathway was Extracellular Matrix Organization, while the most significantly enriched KEGG Pathways were Butanoate metabolism and Synthesis and Degradation of Ketone Bodies. qPCR analysis of weight-matched ELA and control enamel organs confirmed that expression of the ameloblast-specific proteins Amelx and Enam were highly upregulated in ELA mice. When evaluating molecular mechanisms for amelogenin upregulation, we found significantly increased expression of Dlx3, while transcripts for clock genes Per1 and Nrd1, which have also positively associated with amelogenin expression, were downregulated. These findings suggest that the developing enamel organs are sensitive to the pressures of early life adversity and produce structural biomarkers in tooth enamel mineral to reflect these changes. Together these results support the possibility that tooth enamel may contain biomarkers of cellular effects associated with systemic early life adversity.
2022-04-05 | GSE199982 | GEO
Project description:Tooth enamel forms in an ephemeral protein matrix where changes in protein abundance, composition and post-translational modifications are critical to achieve healthy enamel properties. Amelogenin (AMELX) with its splice variants is the most abundant enamel matrix protein, with only one known phosphorylation site at serine 16 shown in vitro to be critical for regulating mineralization. The phosphorylated form of AMELX stabilizes amorphous calcium phosphate, while crystalline hydroxyapatite forms in the presence of the unphosphorylated protein. While it is necessary to our understanding of how AMELX regulates mineral transitions over space and time, it is unknown whether and when un-phosphorylated amleogenin occurs during enamel mineralization. This study aims to reveal the spatiotemporal distribution of the most abundant AMLEX splice variants including the full length P173, the shorter leucine-rich amelogenin protein (LRAP), and the exon 4-containing P190 in forming enamel, all within the context of the changing enamel matrix proteome during mineralization. We microsampled permanent pig molars, capturing known stages of enamel formation from both crown surface and inner enamel. Nano-LC-MS/MS proteomic analyses after tryptic digestion rendered more than 500 unique protein identifications in enamel, dentin, and bone. We mapped collagens, keratins, and proteolytic enzymes (CTSL, MMP2, MMP10) and determined distributions of P173, LRAP and P190, the enamel proteins enamelin (ENAM) and ameloblastin (AMBN), and matrix-metalloprotease-20 (MMP20) and kallikrein-4 (KLK4). All enamel proteins and KLK4 were near-exclusive to enamel and in excellent agreement with published expression levels. Phosphorylated P173 and LRAP decreased in abundance from recently deposited matrix towards older enamel, mirrored by increasing abundances of testicular acid phosphatase (ACPT). Our results showed that hierarchical clustering analysis of secretory enamel links closely matching distributions of unphosphorylated P173 and LRAP with ACPT and nontraditional amelogenesis proteins, many associated with enamel defects. We report higher protein diversity than previously published and Gene Ontology (GO)-defined protein functions related to the regulation of mineral formation in secretory enamel (e.g. casein α-S1, CSN1S1), immune response in erupted enamel (e.g. peptidoglycan recognition protein, PGRP), and phosphorylation. This study presents a novel approach to characterize and study functional relationships through spatiotemporal mapping of the ephemeral extracellular matrix proteome.
2019-07-19 | PXD013604 | Pride
Project description:Organoid models provide powerful tools to study tissue biology and development in a dish. Here, we established first-time organoid models from early-postnatal (postnatal day 7) mouse molar and incisor, capable of differentiation toward ameloblast-like cells in vitro. To more in detail characterise organoids from mouse molar and incisor, bulk RNA-sequencing was performed on the following (1) early passage (passage 0) organoids from both tooth types grown in basal tooth organoid medium (TOM) with or without addition of exogenous epidermal growth factor (EGF); and (2) late passage (passage 5) organoids grown in TOM+EGF or differentiation medium (DM).
2023-04-19 | E-MTAB-12557 | biostudies-arrayexpress
Project description:The enamel proteome includes a range of proteins which are well-preserved in archaeological settings but have so far received less study than the sex-specific sequencing of enamel. We look beyond sex-specific sequencing of amelogenin to investigate the potential of several serum proteins, including immunoglobulin gamma (IgG), the major immunoglobulin found in blood serum, and C-reactive protein (CRP) which is associated with inflammatory response, to provide insight into the health and stresses experienced by individuals in the past. We apply this approach to enamel samples from Mission-Period ancestral Ohlone interred at Asistencia San Pedro y San Pablo (CA-SMA-71/H; n=11). For comparison, we also examine enamel from historic-period European-Americans interred in the City Cemetery in San Francisco, and extracted third molars from present-day military cadets. Results indicate that IgG is elevated among individuals at the asistencia relative to samples from present-day military cadets (n=8), or historic City Cemetery individuals (ANOVA with post-hoc Tukey Kramer tests, p < 0.02). Further, the inflammatory protein CRP, normally expressed at much lower levels than IgG, was present in 55% (6 of 11) of the asistencia samples, and in 17% (2 of 12) of the historic City Cemetery samples, but was not detected in enamel samples from contemporary military cadets. While more studies are needed, we argue that the difference in IgG could reflect higher levels of chronic diseases such as tuberculosis among Ohlone living within the Mission system, while the presence of measurable amounts of CRP could relate to high degrees of physical, social, and emotional stresses. To our knowledge, this is the first paleoproteomic study of immune proteins in tooth enamel. The ability to track immune responses during tooth formation could provide valuable and high-resolution information on ancient health and disease at the level of the individual over archaeological time-scales.
2024-10-09 | PXD054717 | Pride
Project description:Molar Hypomineralization is a developmental enamel defect, characterized by demarcated opacities, hypersensitivity, and soft enamel with elevated protein content. Excess protein in enamel, specifically albumin, not only arrests crystal growth during enamel development but also decreases the success rate of current restorative approaches. The development of targeted treatment options for MH is hampered by scarcity of available human samples to develop and test new treatment approaches. Additionally, there is still a need for an animal model mimicking the human MH phenotype in enamel composition and tooth size. We propose herein deciduous porcine enamel as a model for demarcated opacities in human enamel, based on its similarity in dimensions, mechanical properties, and, in particular, protein composition. In this project we aimed to characterize the distribution and developmental origins of albumin in porcine enamel.
2024-01-26 | PXD030329 | Pride