From Bite to Byte: Dental Structures Resolved at a Single-Cell Resolution.

The systematic classification of the cells that compose a tissue or an organ is key to understanding how these cells cooperate and interact as a functional unit. Our capacity to detect features that define cell identity has evolved from morphological and chemical analyses, through the use of predefined genetic markers, to unbiased transcriptomic and epigenetic profiling. The innovative technology of single-cell RNA sequencing (scRNA-seq) enables transcriptional profiling of thousands of individual cells. Since its development, scRNA-seq has been extensively applied to numerous organs and tissues in a wide range of animal models and human samples, thereby providing a plethora of fundamental biological insights into their development, homeostasis, and pathology. In this review, we present the findings of 3 recent studies that employed scRNA-seq to unravel the complexity of cellular composition in mammalian teeth. These findings offer an unprecedented catalogue of cell types in the mouse incisor, which is a convenient model system for studying continuous tooth growth. These studies identified novel cell types in the tooth epithelium and mesenchyme, as well as new markers for known cell types. Computational analyses of the data also uncovered the lineage and dynamics of cell states during ameloblast and odontoblast differentiation during both normal homeostasis and injury repair. The transcriptional differences between the mouse incisor and mouse and human molars uncover species-specific as well as shared features in tooth cell composition. Here, we highlight these findings and discuss important similarities and differences between these studies. We also discuss potential future applications of scRNA-seq in dental research and dentistry. Together, these studies demonstrate how the rapidly evolving technology of scRNA-seq can advance the study of tooth development and function and provide putative targets for regenerative approaches.

Genetic control of HLA-linked immune responsiveness to (H,G)-A-L.

Fifty-three donors belonging to seven families were tested for their immune response potential to (H,G)-A-L. Most of these donors had been previously tested for their ability to respond to (T,G)-A-L and were all HLA typed as well. The heredity of the ability to respond to (H,G)-A-L by the production of an antigen-specific helper T cell factor is compatible with an autosomal dominant trait linked to HLA. The genotype of an HLA-A/B recombinant individual suggested that a gene controlling the immune response to (H,G)-A-L is linked to HLA-A. Lod scores also suggested a linkage between immune response potential to (H,G)-A-L and HLA-A. The different patterns of responses to (T,G)-A-L and (H,G)-A-L observed in many individuals are compatible with the notion that separate loci are governing the immune responses to the two synthetic polypeptides.

Hypodontia: a polygenic trait--a family study among Israeli Jews.

A high prevalence of hypodontia was detected among 820 first degree relatives of 305 probands and there was an increased risk if a second family member was affected. Hypodontia is a common trait in the population, and a deviation from normal sex ratio was observed in those affected. These results suggest a polygenic mode of inheritance.

Amelogenesis imperfecta among Israeli Jews and the description of a new type of local hypoplastic autosomal recessive amelogenesis imperfecta.

Amelogenesis imperfecta (AI) was detected in nine of 70,359 school children surveyed, a prevalence approximating 1:8,000. Of these cases, eight were the hypoplastic type and one the snow-capped hypomaturation type. Family studies demonstrated that hypoplastic AI was an autosomal dominant trait in two children and an autosomal recessive in six. Of three additional families referred to our clinic, two had autosomal recessive hypoplastic AI and one the hypocalcified type, inherited as an autosomal dominant trait. In four families, a new type of local hypoplastic autosomal recessive AI was observed, characterized by horizontal pitting and grooving more pronounced in the middle third of the crowns of most teeth in both dentitions.

A rapid epidemiological assessment of dental erosion to assist in settling an industrial dispute.

A rapid epidemiological assessment (REA) of industrial dental erosion was undertaken with the aim of formulating a range of treatment strategies which could be used to settle an industrial dispute. This dispute concerned compensation for a group of adult male metalworkers who had complained of dental sensitivity and that their teeth had been "eaten by acid" at their workplace, an electroplating factory in Springs near Johannesburg, South Africa. The REA methods employed included a clinical examination, a structured socio-demographic questionnaire and colour photographs of each subject. Sixty per cent of the subjects reported pain and/or sensitivity to eating and/or drinking, 76 per cent showed varying degrees of loss of tooth structure, and 25 per cent reported teeth had been lost as a result of the industrial erosion. The project involved negotiating with mine management and trade union representatives, each with conflicting interests, and with people's oral health and large sums of money at stake. In this context, the aim of the research was to design an instrument to resolve conflict and to promote oral health at an industrial site, while retaining scientific objectivity and rigour. As a result of the REA, the workers who were examined are in the process of being compensated, while the National Union of Mineworkers and mine management are engaged in reaching a settlement. Preventive measures have been initiated at the factory. The area has been declared a "respiratory zone", which makes the wearing of respiratory masks obligatory.

Transesophageal defibrillation: animal studies and preliminary clinical observations.

Ventricular fibrillation (VF) that fails to respond to transthoracic defibrillation leaves the clinician with few alternatives. The purpose of this study was to develop a technique of rescue defibrillation by use of transesophageal electrodes. Fourteen anesthetized dogs (20-30 kg) were investigated in this study. Two electrodes (300 mm2) were mounted 8 cm apart on an esophageal probe and inserted approximately 40 cm from the mouth. VF was induced using AC current delivered to the myocardium. Defibrillation was then performed between the distal electrode (anode) and anterior skin patch (cathode). After 15 seconds of induced VF, transesophageal and transthoracic defibrillation thresholds (DFTs) were determined in random order. The esophageal DFT (90 +/- 15 joules) tended to be lower than the transthoracic DFT (115 +/- 35 joules), though this difference was not statistically significant. One dog could not be defibrillated by transthoracic defibrillation but responded to transesophageal defibrillation. Esophageal electrodes were also useful for arrhythmia discrimination and ventricular pacing (pacing threshold of 38 +/- 5 mA at a pulse duration of 2.5 msec). Following transesophageal DFT determination, in ten dogs (total energy of 600 +/- 150 joules), acute esophageal histopathology demonstrated mild to severe focal injury to the mucosa and/or muscular layers. However, esophagi in four chronic dogs (total energy of 470 +/- 110 joules) showed no gross evidence of mucosal damage, perforation, or stricture 4 weeks following defibrillation. Histopathology showed only focal myocyte atrophy and repair. As a last resort, transesophageal defibrillation was performed in the emergency room on four patients with out-of-hospital refractory VF who failed > 6 high energy transthoracic shocks.(ABSTRACT TRUNCATED AT 250 WORDS)