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Epithelial Stem Cell Migration during Wound Repair

伤口修复过程中上皮干细胞的迁移

基本信息

批准号：
8434080
负责人：
Catherine Pei-Ju Lu
金额：
$ 5.77万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434080
关键词：
Accounting Address Adult Area Behavior Binding Bioinformatics Biological Assay Cell Adhesion Molecules Cell Proliferation Cell Surface Receptors Cells Data Dehydration Embryo Engraftment Epidermis Epithelial Equilibrium Exhibits Extracellular Matrix Focal Adhesion Kinase 1 Gene Expression Generations Genes Genetic Transcription Growth Factor Hair follicle structure Homeostasis Image Immigration Immunohistochemistry In Situ Hybridization In Vitro Injury Integrins Knowledge Left Methods Molecular Molecular Profiling Monitor Mus Natural regeneration Neoplasm Metastasis Pattern Physiological Play Population Process Regenerative Medicine Relative (related person)Research Research Proposals Rest Role Sebaceous Glands Signal Pathway Signal Transduction Site Skin Stem cells Stratum Basale Structure Structure of infundibulum of hair follicle Testing Time Tissues Transgenic Mice Wild Type Mouse Wound Healing cancer stem cell cell motility comparative design genome-wide in vivo insight keratinocyte differentiation knock-down migration mouse model novel pathogen prevent public health relevance repaired research study response response to injury self-renewal small hairpin RNA stem cell population tumor tumor progression wound

项目摘要

DESCRIPTION (provided by applicant): Upon injury, the skin epidermis must undergo immediate repair mechanism to restore its barrier function to prevent dehydration and invasion of harmful pathogens. Wound repair of the skin epidermis involves activation, migration, proliferation, and differentiation of keratinocytes. In particular, the re-epithelialization of the wounded area requires skin epithelial stem cells, which migrate in both from the surrounding epidermis and also from the hair follicle. However, very little is known about the signals that activate stem cell migration and the molecular mechanisms directing their migration during wound repair. How do hair follicle stem cells respond to wound signals? What are the signaling pathways that direct stem cell migration during wound repair? Which population(s) of epithelial stem cells is responsible for repairing the epidermis and generation of new hair follicles? In this research plan, I propose to: (1) Identify the cells within the hair follicle that contribute to wound repair; (2) Purify and characterize the cells within the hair follicle that contribute to wound repair; (3) Monitor and characterize cells as they migrate during wound repair; and (4) Perform functional studies on molecules that may be involved in cell migration and re-epithelialization during wound repair. I plan to exploit mouse models that allow lineage tracing of skin stem cells and their progeny during the process of wound healing. This enables characterization and isolation of skin stem cells that contribute to wound repair and generation of new hair follicles. A genome-wide gene profiling will be conducted to examine the changes in gene expression, and to identify molecules and signal pathways that may be involved in migration of the skin stem cells. I will perform further functional assays to validate the participation of the candidate molecules in the migration process. Findings from this research plan will contribute to our understanding of the molecular mechanism of skin stem cell migration upon injury and provide answers to many fundamental questions in the stem cell field.

描述（申请人提供）：皮肤表皮受伤后必须立即进行修复机制，恢复其屏障功能，防止脱水和有害病原体入侵。皮肤表皮的创伤修复涉及角质形成细胞的活化、迁移、增殖和分化。特别地，受伤区域的再上皮化需要皮肤上皮干细胞，其从周围表皮和毛囊两者中迁移。然而，很少有人知道的信号，激活干细胞迁移和分子机制，指导他们在伤口修复迁移。毛囊干细胞如何响应伤口信号？在创伤修复过程中，指导干细胞迁移的信号通路是什么？哪些上皮干细胞群负责修复表皮和产生新的毛囊？在本研究计划中，我建议：（1）识别毛囊内有助于伤口修复的细胞;（2）纯化和表征毛囊内有助于伤口修复的细胞;（3）监测和表征伤口修复期间迁移的细胞;（4）对可能参与伤口修复期间细胞迁移和再上皮化的分子进行功能研究。我计划开发小鼠模型，允许皮肤干细胞及其后代在伤口愈合过程中的谱系追踪。这使得能够表征和分离有助于伤口修复和产生新毛囊的皮肤干细胞。将进行全基因组基因分析，以检查基因表达的变化，并确定可能参与皮肤干细胞迁移的分子和信号通路。我将进行进一步的功能分析，以验证候选分子在迁移过程中的参与。这项研究计划的发现将有助于我们理解皮肤干细胞在损伤后迁移的分子机制，并为干细胞领域的许多基本问题提供答案。