Fibroblast Growth Factor Signaling in Odontogenic Epithelial Stem Cells

牙源性上皮干细胞中的成纤维细胞生长因子信号传导

• 批准号: 8740696
• 负责人: FEN WANG
• 金额: $ 28.48万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-28 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8740696
• 关键词: 3-Dimensional; Ablation; Adaptor Signaling Protein; Affect; Alleles; Biomedical Engineering; Cell Culture System; Cell Culture Techniques; Cell Lineage; Cell Maintenance; Cell Survival; Cell physiology; Cells; Cervical; Communities; Defect; Development; Developmental Process; Engineering; Epithelial; Epithelial-Stromal Communication; Epithelium; FGFR1 gene; FGFR2 gene; FRS2 gene; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Future; Genetically Engineered Mouse; Goals; Growth; Growth Factor Receptors; Health; Heparitin Sulfate; Homeostasis; Human; In Vitro; Incisor; Laboratories; Life; Ligands; Light; Link; Longevity; MAP Kinase Gene; Maintenance; Mandible; Maxilla; Mediating; Mesenchymal; Mesenchymal Stem Cells; Methods; Molecular; Mus; Nanotechnology; Natural regeneration; Odontoblasts; Odontogenesis; Odontogenic Tumors; Outcome Study; PI3K/AKT; Pathogenesis; Pathway interactions; Phenotype; Phosphotransferases; Play; Population; Public Health; Receptor Cell; Receptor Signaling; Regenerative Medicine; Regulation; Reproduction; Research; Role; Signal Pathway; Signal Transduction; Solid; Solutions; Stem Cell Research; Stem cells; Suspension Culture; System; Technology; Tooth structure; Woman; base; cofactor; improved; innovation; men; mouse model; novel; novel strategies; public health relevance; receptor; receptor expression; restoration; self-renewal; stem cell niche

DESCRIPTION (provided by applicant): Defective and damaged teeth are a common public health problem affecting the majority of human being throughout their lifespan. Tooth bioengineering and regeneration can have a premise future to tackle this health issue. A thorough understanding of molecular and cellular processes that regulate tooth stem cell self-renewal and differentiation is crucial to build new teeth. Currently, significant progresses have been made in tooth mesenchymal stem cells research. Yet, odontogenic epithelial stem cells (OESCs) are understudied and no suitable in vitro culture system is available for expansion and analyses of OESCs. The fibroblast growth factor (FGF) signaling axis has been shown plays important roles in development and survival of the cervical loop, a stem cell niche that supports the lifelong growth of mouse incisors. In this project, we will use the newly developed in vitro culture systems for OESCs and the genetically engineered mouse models to study the mechanisms that underlie regulation of survival, self- renewal, and differentiation of OESCs by the FGF signaling axis. We will first optimize the OESC sphere culture conditions, and study how to induce OESC lineage commitment and differentiation by manipulation of the FGF signaling axis. Next, we will develop methods for enriching OESCs and for lineage tracing of OESC progeny. We will then determine whether the FGF signaling axis is required for the survival, self-renewal, and differentiation of OESCs. These studies will advance our understanding of how self-renewal, expansion, and differentiation are regulated in general; the findings will likely benefit a large number of men and women with defective or damaged teeth, and will guide future efforts aimed at stem cell-based tooth bioengineering. The project is highly innovative since it is the first to understand how survival, self-renewal, and differentiation of OESC are regulated. Novel genetically engineered mouse models and novel OESC culture systems will be developed, which, together with currently available ones, will also benefit the tooth research community.

描述（由申请人提供）：有缺陷和受损的牙齿是影响大多数人类一生的常见公共卫生问题。牙齿生物工程和再生可以有一个前提来解决这个健康问题。对调节牙齿干细胞自我更新和分化的分子和细胞过程的透彻理解对于构建新牙齿至关重要。当前，在牙齿间充质干细胞研究中已经取得了重大进展。然而，牙源性上皮干细胞（OESC）被研究研究，并且没有适合OESC的扩展和分析的体外培养系统。已经显示出成纤维细胞生长因子（FGF）信号轴在宫颈环的发育和存活中起着重要作用，这是一种支持小鼠门牙终身生长的干细胞生态位。在该项目中，我们将使用新近开发的OESC的体外培养系统和基因工程的小鼠模型来研究生存，自我更新和通过FGF信号轴对OESC进行调节的机制。我们将首先优化OESC球体培养条件，并研究如何通过操纵FGF信号轴诱导OESC谱系承诺和分化。接下来，我们将开发丰富OESC和OESC后代谱系追踪的方法。然后，我们将确定FGF信号轴是否需要生存，自我更新和OESC的分化。这些研究将促进我们对自我更新，扩张和分化的一般调节的理解。这些发现可能会使大量牙齿有缺陷或受损的男人和女性受益，并将指导针对基于干细胞的牙齿生物工程的未来努力。该项目具有很高的创新性，因为它是第一个了解OESC的生存，自我更新和差异化的方式。新型基因工程的小鼠模型和新型的OESC培养系统将被开发出来，该系统将与当前可用的培养系统一起受益。