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

基本信息

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
项目类别：
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

项目摘要

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）：牙齿缺陷和损坏是影响大多数人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未来来解决这个健康问题。彻底了解调节牙齿干细胞自我更新和分化的分子和细胞过程对于构建新牙齿至关重要。目前，牙齿间充质干细胞研究已取得重大进展。然而，牙源性上皮干细胞 (OESC) 的研究尚未充分，并且没有合适的体外培养系统可用于 OESC 的扩增和分析。成纤维细胞生长因子 (FGF) 信号轴已被证明在颈环的发育和存活中发挥重要作用，颈环是支持小鼠门牙终生生长的干细胞生态位。在这个项目中，我们将利用新开发的OESC体外培养系统和基因工程小鼠模型来研究FGF信号轴调节OESC生存、自我更新和分化的机制。我们将首先优化 OESC 球体培养条件，并研究如何通过操纵 FGF 信号轴来诱导 OESC 谱系定型和分化。接下来，我们将开发富集 OESC 和 OESC 后代谱系追踪的方法。然后我们将确定 FGF 信号轴是否是 OESC 的生存、自我更新和分化所必需的。这些研究将增进我们对自我更新、扩张和分化一般如何调节的理解；这些发现可能会使大量牙齿有缺陷或受损的男性和女性受益，并将指导未来基于干细胞的牙齿生物工程的努力。该项目具有高度创新性，因为它是第一个了解 OESC 的生存、自我更新和分化如何调节的项目。将开发新型基因工程小鼠模型和新型 OESC 培养系统，与现有的系统一起，也将使牙齿研究界受益。