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Hair follicle bulge cells in tumorigenesis and alopecia

肿瘤发生和脱发中的毛囊凸出细胞

基本信息

批准号：
7929359
负责人：
GEORGE COTSARELIS
金额：
$ 25.2万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2009-09-18 至 2011-09-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7929359
关键词：
Alopecia Applications Grants Basal cell carcinoma Biological Assay Candidate Disease Gene Cell Count Cell Cycle Cell Separation Cell Surface Proteins Cells Characteristics Chronic Cornea Cutaneous Disease Dominant-Negative Mutation Epidermis Epithelial Epithelium Funding Future Gene Expression Generations Genes Germ Goals Hair Hair Follicle Neoplasm Hair follicle structure Hair shaft structure Human Keratin Molecular Molecular Analysis Mus Natural regeneration Nature Pathway interactions Patients Pattern Phenotype Plant Roots Play Positioning Attribute Property RU-486 Research Role Sebaceous Glands Skin Skin Physiology Specificity Stem cells System Testing Tissues Transgenic Mice Wound Healing base cDNA Arrays carcinogenesis gene discovery gene function insight overexpression progenitor promoter protein expression reconstitution self-renewal skin disorder stem stem cell biology tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this project is to better understand epithelial stem cell biology. Epithelial stem cells are responsible for the regeneration of self-renewing tissues such as epidermis, hair follicle, and cornea. We originally identified putative epithelial stem cells in the bulge of the hair follicle. We then isolated a keratin 15 promoter that targets bulge cells in transgenic mice. The K15 promoter allowed for the isolation, lineage analysis and molecular characterization of hair follicle stem cells. We showed, that bulge cells have properties of stem cells, and isolated bulge cells can reconstitute hair follicles, epidermis and sebaceous glands. We have now identified a number of genes which we hypothesize maintain the stem cell phenotype. In this grant application we will: 1. evaluate whether genes upregulated in the bulge cells are important for maintaining the hair follicle stem cell phenotype by: a. overexpressing candidate genes in non-hair follicle stem cells of transgenic mice, and then testing whether these cells behave as hair follicle stem cells. b. blocking candidate gene pathways specifically in the bulge cells using our Kl5CrePrl mice to delete or overexpress genes specifically in the bulge cells. 2. determine if genes downregulated in telogen bulge cells are involved in stem cell activation and/or lineage determination by: a. generating inducible transgenic mice in which candidate genes are over-expressed in bulgecells using an RU486 inducible system, and b. deleting candidate "bulge activation" or lineage determining genes specifically in bulge cells and their progeny using theKlSCrePR l mice. 3. develop means for isolating and characterizing human hair follicle stem cells. a. We will establish whether genes identified in mouse bulge are also expressed in human bulges. b. We will delineate hair follicle stem and progenitor cells within both the mouse and human hair follicle based on cell surface protein expression patterns. These distinct subpopulations of cells within the hair follicle will be isolated by fluorescent activated cell sorting, and their stem cell nature, gene expression patterns and functional characteristics will be discerned. Patients with alopecia, hair shaft disorders, basal cell carcinoma, hair follicle tumors, or chronic wounds could potentially benefit from this research.

描述（由申请人提供）：该项目的长期目标是更好地了解上皮干细胞生物学。上皮干细胞负责自我更新组织的再生，如表皮、毛囊和角膜。我们最初在毛囊凸起处发现了假定的上皮干细胞。然后，我们在转基因小鼠中分离出一个角蛋白15启动子，该启动子针对凸起细胞。K15启动子可用于毛囊干细胞的分离、谱系分析和分子表征。我们发现，膨出细胞具有干细胞的特性，分离的膨出细胞可以重建毛囊、表皮和皮脂腺。我们现在已经确定了一些我们假设维持干细胞表型的基因。在这项拨款申请中，我们会：

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Review of hair follicle dermal cells.

DOI：
10.1016/j.jdermsci.2009.11.005
发表时间：
2010-01
期刊：
Journal of dermatological science
影响因子：
4.6
作者：
Yang CC;Cotsarelis G
通讯作者：
Cotsarelis G

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.

DOI：
10.1126/scitranslmed.3003122
发表时间：
2012-03-21
期刊：
Science translational medicine
影响因子：
17.1
作者：
Garza LA;Liu Y;Yang Z;Alagesan B;Lawson JA;Norberg SM;Loy DE;Zhao T;Blatt HB;Stanton DC;Carrasco L;Ahluwalia G;Fischer SM;FitzGerald GA;Cotsarelis G
通讯作者：
Cotsarelis G

Epidermal cells rev up reprogramming.

表皮细胞加速重新编程。