RAS Signaling in Skin Stem Cell Proliferation and Fate

皮肤干细胞增殖和命运中的 RAS 信号转导

基本信息

批准号：
8256556
负责人：
BENJAMIN DIUNG-YUEN YU
金额：
$ 29.73万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8256556
关键词：
Affect Age Alleles BRAF gene Cell Cycle Cell Cycle Arrest Cell Cycle Regulation Cell Differentiation process Cell Proliferation Cells Child Defect Development Epidermis Erinaceidae Experimental Models Failure Foundations Future Gene Expression Genetic Models Goals Growth Growth and Development function Hair Hair follicle structure Health Homeostasis Human Human Genetics KRAS2 gene Laboratories Laboratory Study MAP Kinase Gene MAP2K1 gene MEKs Modeling Mus Mutation Natural regeneration Pathway interactions Patients Physiological Play Production Regenerative Medicine Regulation Role Signal Pathway Signal Transduction Skin Skin Abnormalities Stem cells Stimulus Syndrome Tissues Work Wound Healing adult stem cell base cardiofaciocutaneous syndrome gain of function improved interest mouse model novel organ regeneration response self-renewal senescence stem cell fate specification

项目摘要

DESCRIPTION (provided by applicant): Adult stem cells are the basic building blocks for wound repair and regeneration. Understanding how to stimulate their growth and development is critical to advancing regenerative medicine. Our laboratory studies adult stem cells in the hair follicle because they are accessible and divide at specific developmental ages. Recently, activating mutations in the RAS signaling pathway have been found in children with Costello and cardiofaciocutaneous (CFC) syndromes. These syndromes are associated with multiple skin defects that appear to affect the proliferation and differentiation of skin stem cells. We have recently developed several mouse models, which develop many of the same skin abnormalities as Costello and CFC patients, including excess skin production and hair loss. We propose to use our mouse models to 1) investigate the basis of RAS- induced hair cycle defects, 2) determine the effect of RAS on adult stem cell proliferation, and 3) identify the downstream pathways that cause these defects. By understanding the function of RAS signaling in adult stem cells of the skin, new therapies could be developed to improve organ regeneration and wound repair. PUBLIC HEALTH RELEVANCE: Adult stem cells are the basic building blocks for wound repair and regeneration. We are studying the role of RAS in regulating adult stem cell proliferation and differentiation. As an experimental model, we will study how RAS affects adult stem cells of the hair follicle during regeneration and wound repair.

描述（由申请人提供）：成年干细胞是伤口修复和再生的基本基础。了解如何刺激其成长和发展对于推进再生医学至关重要。我们的实验室研究成年毛囊中的成年干细胞是因为它们可以进入并在特定的发育年龄分开。最近，在患有Costello和心faciociociatanous（CFC）综合征的儿童中发现了RAS信号通路中的激活突变。这些综合征与多种皮肤缺陷有关，这些缺陷似乎影响了皮肤干细胞的增殖和分化。我们最近开发了几种小鼠模型，它们与Costello和CFC患者相同的皮肤异常，包括皮肤生产过多和脱发。我们建议使用小鼠模型1）研究RAS诱导的头发周期缺陷的基础，2）确定RAS对成年干细胞增殖的影响，3）确定导致这些缺陷的下游途径。通过了解RAS信号在皮肤成年干细胞中的功能，可以开发出新的疗法来改善器官再生和伤口修复。公共卫生相关性：成年干细胞是伤口修复和再生的基本基础。我们正在研究RA在调节成年干细胞增殖和分化中的作用。作为实验模型，我们将研究RAS在再生和伤口修复过程中如何影响毛囊的成年干细胞。