Microenvironment Regulation of Epidermal Stem Cells

表皮干细胞的微环境调节

• 批准号: 7278660
• 负责人: ADAM M GIANGRECO
• 金额: $ 4.18万
• 依托单位: CANCER RESEARCH UNITED KINGDOM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278660
• 关键词: Affect; Cell Differentiation process; Cell Mobility; Cell Proliferation; Cells; Collection; Daughter; Dehydration; Dominant-Negative Mutation; Emigrations; Epidermis; Epithelial; Fellowship; Gene Expression Profiling; Generations; Genetic; Hair follicle structure; Heterogeneity; Individual; Infection; Injury; Localized; Maintenance; Mitotic; Modeling; Mus; Natural regeneration; Numbers; Oncogenic; Outcome; Pathway interactions; Phenotype; Play; Population; Protein Overexpression; Proteins; Regulation; Residencies; Role; Sebaceous Glands; Signal Transduction; Skin; Stem cells; Tissues; Transgenic Mice; Transplantation; bone morphogenic protein; comparative; keratinocyte; laser capture microdissection; migration; protein expression; receptor; smoothened signaling pathway; stem cell fate; tumor

DESCRIPTION (provided by applicant): The epidermis of mammalian skin is a collection of individual keratinocytes acting in concert to provide a protective barrier against injury, infection, and dehydration. Normal function is maintained through regeneration originating within basally located keratinocyte stem cells. It is generally accepted that microenvironment-dependent activation of epidermal stem cells is necessary to maintain their multipotency. In addition to regulating the fate of normal stem cells, local microenvironmental influences affect the outcome of various stem cell-derived epidermal tumors. This suggests that the local microenvironment plays a dominant role in the regulation of epidermal stem cells. Specific aim I will identify factors that define active stem cell microenvironments through laser capture microdissection and gene expression profiling. Specific aim 2 will determine the necessity of microenvironment association in maintenance of stem cell potency through the generation of transgenic mice overexpressing the promigratory DeltaT protein specifically within epidermal stem cells. Specific aim 3 will determine whether the local microenvironment is sufficient to regulate stem cell differentiation potential using interfollicular stem cell-follicular microenvironment grafts.

描述（由申请人提供）：哺乳动物皮肤的表皮是单个角质形成细胞的集合，其共同作用以提供针对损伤、感染和脱水的保护屏障。正常的功能通过起源于位于基底的角质形成细胞干细胞内的再生来维持。人们普遍认为，表皮干细胞的微环境依赖性激活是维持其多能性所必需的。 除了调节正常干细胞的命运外，局部微环境影响影响各种干细胞衍生的表皮肿瘤的结果。这表明局部微环境在表皮干细胞的调节中起主导作用。具体目标我将通过激光捕获显微切割和基因表达谱来确定定义活跃干细胞微环境的因素。具体目标2将确定微环境关联在通过产生在表皮干细胞内特异性过表达促迁移DeltaT蛋白的转基因小鼠来维持干细胞效力中的必要性。具体目标3将确定局部微环境是否足以使用滤泡间干细胞-滤泡微环境移植物调节干细胞分化潜能。