Regulation of Sebaceous Gland Development

皮脂腺发育的调节

基本信息

批准号：
8011731
负责人：
Valerie Horsley
金额：
$ 23.68万
依托单位：
YALE UNIVERSITY
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：
2009-04-01 至 2011-12-31
项目状态：
已结题

项目摘要

The long-term goal of this proposal is to understand the regulation of epithelial stem cell commitment to the sebaceous gland lineage. The sebaceous gland develops along with the hair follicle as epidermal stem cells commit to a particular lineage and differentiate. When sebaceous development is aberrant, two unsolved dermatological pathologies, acne vulgaris and human tumors, develop. Yet, despite the clinical importance of this cell lineage in human disease, little Is known about how this lineage forms. My prelimary data identifies a population of unipotent progenitor cells that by expression of the transcriptional repressor, Blimpl, regulates the cellular Input into the sebaceous gland and elicits premature activity of epithelial stem cells. The central hypothesis tested by this proposal is that the formation of sebaceous progenitors from hair follicle stem cells is crucial for proper formation and biology of the sebaceous gland. This hypothesis will be tested in this grant application by experiments: 1) identifying mechanisms that regulate progenitor fate by Blimpl, and 2) determining the role of sebaceous progenitors in communication with the hair follicle stem cell compartment. During the mentored phase of this award, I have identified a number of potential mechanisms that regulate sebaceous gland developoment and will follow-up on particular genes identified and cellular mechanisms will be performed in the independent phase of this proposal. Data generated from the proposed experiments will advance our understanding of the mechanisms regulating sebaceous gland development and and stem cell lineage commitment in the skin. In addition, these proposed studies will potentially lead to the development of therapeutic treatments for disorders of the sebaceous gland as well as other skin disorders and cancers.

该提案的长期目标是了解对皮脂腺谱系上皮干细胞承诺的调节。皮脂腺随着表皮干细胞致力于特定的谱系和分化而与毛囊一起发展。当皮脂腺发育异常时，会出现两种未解决的皮肤病学病理学，痤疮和人类肿瘤。然而，尽管该细胞谱系在人类疾病中具有临床重要性，但对这种谱系的形成方式知之甚少。我的初步数据确定了一支单位祖细胞的群体，通过表达转录阻遏物Blimpl，调节细胞输入到皮脂腺中，并引起上皮干细胞的过早活性。该提议检验的中心假设是，毛囊干细胞中皮脂腺祖细胞的形成对于皮脂腺的正确形成和生物学至关重要。该假设将通过实验在此赠款应用中进行测试：1）识别通过Blimpl调节祖细胞命运的机制，以及2）确定皮脂腺祖细胞在与毛囊干细胞室通信中的作用。在该奖项的指导阶段，我已经确定了许多潜在的机制，这些机制调节皮脂腺的发展，并将对所鉴定的特定基因进行跟进，并将在本提案的独立阶段进行细胞机制。根据提出的实验产生的数据将提高我们对调节皮脂腺发育以及皮肤中干细胞谱系承诺的机制的理解。此外，这些提出的研究将有可能导致对皮脂腺疾病以及其他皮肤疾病和癌症的治疗治疗的发展。