Fibroblast Growth Factor signaling in odontogenic epithelial stem/progenitor cell

牙源性上皮干细胞/祖细胞中的成纤维细胞生长因子信号传导

• 批准号: 8588542
• 负责人: Julia Yu Fong Chang
• 金额: $ 9.55万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588542
• 关键词: Fibroblast; Growth; Factor; signaling; odontogenic

DESCRIPTION (provided by applicant): The long term objectives of this new K08 application are to develop the applicant's expertise to conduct independent and creative research in an area of oral biomedical sciences that is relevant to the specialty of Oral Pathology. Support for five years, including three years of formal research training towards a Ph.D. degree is requested. The candidate was a former oral pathology resident at the Baylor College of Dentistry and will expand upon her scientific skills through a unique integration of interdepartmental resources. The career development plan proposes a phased and integrated series of didactic instruction and supervised research training. This program will promote the understanding of stem cell and developmental biology, as applied to dentistry and future oral pathology. Dr. Fen Wang will mentor the principal investigator's scientific development. Dr. Wang is a recognized leader in the field of fibroblast growth factor (FGF) in developmental and cancer biology. He has trained numerous postdoctoral fellows and graduate students. To enhance the training, the program will enlist the expertise of Dr. D'Souza, Biomedical Science Chair, and Dr. Wright, Oral Pathology Chair. Research will focus on the roles of FGF in regulating the capability of self-renewal and differentiation in the odontogenic epithelial stem cells. The specific aims include: 1) characterize the cells and signaling in cervical loop region be affected in Fgfr2 tissue specific knockout mice during incisor development; 2) establish an odontogenic epithelial stem cell culture system; 3) determine the role of FGF/FGFR2/FRS21/MAPK signaling in self-renewal and differentiation of cervical loop odontogenic epithelial stem cells in 3D in vitro sphere culture. This will be the first establishment of odontogenic epithelial stem cell culture and detailed functional analysis of FGF using 3D in vitro sphere culture. These data will provide new insights into the role of FGF in regulating odontogenic epithelial stem cells and for future regeneration. The combination of the Institute of Biosciences and Technology and the biomedical sciences and oral pathology departments of Baylor College of Dentistry provides an ideal setting for training dentist-scientists by incorporating expertise from diverse resources into customized programs. Valuable knowledge can be gained from the research directed towards the development of regeneration application to aid in the prevention and treatment of odontogenic lesions and tumors in the future. Public Health Relevance: Stem cells derived from both epithelial and mesenchymal components are required for future regeneration of whole teeth. The key for reconstruction from defined cellular and molecular components and further elucidating the alterations in pathology depends on developing in vitro systems that accurately recapitulate the in vivo functions. Although Fibroblast Growth Factors (FGF) have been shown to play important roles in maintenance of the mouse incisor cervical loop region where stem cells are thought to reside, the defined mechanism of FGF signaling is not yet available for the odontogenic epithelial stem cells and surrounding microenvironment. Our project is aimed at defining the FGF signaling pathways for the odontogenic epithelial stem cells derived from mouse incisor cervical loops through an in vivo Fgfr2 tissue specific knockout mouse model and developing in vitro sphere culture model.

描述（由申请人提供）：本新K08申请的长期目标是开发申请人的专业知识，以在口腔生物医学科学领域进行独立和创造性研究，该研究与口腔病理学专业有关。支持五年的支持，包括三年的正式研究培训。要求学位。该候选人是贝勒牙科学院的前口腔病理学居民，将通过独特的部门间资源融合来扩展她的科学技能。职业发展计划提出了一系列分阶段和集成的教学教学和监督研究培训。该计划将促进对干细胞和发育生物学的理解，以应用于牙科和未来的口腔病理。 Fen Wang博士将指导主要研究者的科学发展。 Wang博士是发育和癌症生物学领域成纤维细胞生长因子（FGF）领域的公认领导者。他已经培训了许多博士后研究员和研究生。为了增强培训，该计划将获得生物医学科学主席D'Souza博士和口腔病理学主席Wright博士的专业知识。研究将集中于FGF在调节牙源性上皮干细胞中自我更新和分化能力方面的作用。具体目的包括：1）在门牙发育过程中，在FGFR2组织特异性基因敲除小鼠中影响宫颈环区域中的细胞和信号传导； 2）建立牙源性上皮干细胞培养系统； 3）确定FGF/FGFR2/FRS21/MAPK信号在3D体外球体培养中的颈环齿状上皮干细胞的自我更新和分化中的作用。这将是使用3D体外球培养的牙源性上皮干细胞培养和FGF的详细功能分析的第一个建立。这些数据将为FGF在调节牙源性上皮干细胞和将来再生中的作用提供新的见解。贝勒牙科学院的生物医学科学研究所以及生物医学科学和口腔病理学系的结合，通过将各种资源的专业知识纳入定制计划，为培训牙医科学家提供了理想的环境。可以从针对再生应用开发的研究中获得宝贵的知识，以帮助预防和治疗未来的牙源性病变和肿瘤。 公共卫生相关性：源自上皮和间质成分的干细胞是整个牙齿的未来再生所必需的。从定义的细胞和分子成分重建的关键以及进一步阐明病理学改变的关键取决于开发精确概括体内功能的体外系统。尽管已经证明成纤维细胞生长因子（FGF）在认为存在于干细胞的小鼠门牙宫颈环区域中起着重要作用，但人们认为干细胞驻留，但FGF信号的定义机制尚不可用于牙源性上皮上皮干细胞和周围的微环境。我们的项目旨在定义通过体内FGFR2组织特异性敲除小鼠模型并发展体外球体培养模型的小鼠切牙宫颈环的牙源性上皮干细胞的FGF信号通路。