Microenvironment Regulation of Epidermal Stem Cells

表皮干细胞的微环境调节

• 批准号: 6944565
• 负责人: ADAM M GIANGRECO
• 金额: $ 0.55万
• 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/6944565
• 关键词: biological signal transduction; cell adhesion; cell differentiation; cell growth regulation; cell migration; developmental genetics; gene expression; gene expression profiling; genetically modified animals; granulosa cell; keratinocyte; laboratory mouse; laser capture microdissection; pluripotent stem cells; postdoctoral investigator; regeneration; skin neoplasms; stem cells

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(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，它们协同作用，提供保护屏障，防止受伤、感染和脱水。正常的功能是通过起源于碱基定位的角质形成干细胞的再生来维持的。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，局部微环境的影响还会影响各种干细胞来源的表皮肿瘤的预后。这表明局部微环境在表皮干细胞的调控中起主导作用。具体目的：我将通过激光捕获、显微解剖和基因表达谱识别定义活跃干细胞微环境的因素。具体目标2将通过产生过度表达表皮干细胞内特异的前游走DeltaT蛋白的转基因小鼠来确定微环境联合在维持干细胞效力方面的必要性。具体目标3将确定局部微环境是否足以调节使用毛囊间干细胞-毛囊微环境移植的干细胞分化潜能。