Molecular mechanisms controlling tooth development

项目总结 遗传性疾病，如牙齿发育不全，牙本质形成不全，感染性疾病，如龋齿或 骨折是常见的公共卫生问题，影响着全球高达30%-40%的人口， 给患者造成重大负担(疾病控制和预防中心，2019年)。估计 牙科疾病的直接成本达3568亿美元，全球因牙科疾病造成的总成本为 2015年为5444.1亿美元。鉴于牙科疾病在普通人群中的流行有增无减，它可以 只能预计，未来的数量和成本将会加剧。 由于牙齿再生仍然难以捉摸，恢复功能和美观是漫长而昂贵的。当前的努力 在再生牙科领域，依赖于可获得的方法将组织注射到体外扩张 异质多能干细胞群体或多能细胞系的体外分化后代。由于 祖细胞来源关于其产生能力的分子特征的描述不足 功能分化的细胞后代，这些努力导致可用于构建新的 纸巾。因此，识别可靠地促使细胞 例如，分化成一种细胞类型而不是另一种细胞类型将填补我们知识中的一个重大缺口，从而可靠地 制定在干细胞治疗中重现这些过程的策略。该项目的目标是确定 决定牙间充质细胞分化和分化的基因和途径的细胞和分子同一性 牙齿发育早期的命运，并利用这一信息开发潜在的主要针对牙本质的治疗方法 再生。

PROJECT SUMMARY Genetic diseases such as tooth agenesis, dentinogenesis imperfecta, infectious diseases such as caries or fractures represent common public health problems that affect up to 30-40% of the population worldwide and impose significant burdens on patients (Centers for Diseases Control and Prevention, 2019). The estimated direct costs of dental diseases amounted to $356.80 billion, totaling worldwide costs due to dental diseases of $544.41 billion in 2015. Given the unabated rise of dental diseases prevalence in the general population, it can only be expected that the number and cost will intensify in the future. As tooth regeneration remains elusive, restoring function and esthetics is lengthy and expensive. Current efforts in the field of regenerative dentistry rely on the availability of methods that inject into tissues in vitro expanded heterogeneous multipotent stem cell populations or in vitro differentiated progeny of pluripotent cell lines. Due to insufficient characterization of the molecular signature of progenitor cell sources as to their capacity to generate functional differentiated cell progeny, these efforts lead to insufficient numbers of cells available for building new tissues. Thus, identifying the cellular and molecular identity of genes and pathways that reliably prompt cells to differentiate into one cell type and not another for instance would fulfil a major gap in our knowledge to reliably develop strategies for recreating these processes in stem cell therapies. The goal of this project is to identify the cellular and molecular identity of genes and pathways defining dental mesenchymal cell differentiation and fate early in tooth development and harness this information to develop potential therapeutics mainly for dentin regeneration.