Inductive properties of the dermal papilla of the hair follicle

毛囊真皮乳头的感应特性

• 批准号: 7299684
• 负责人: BRUCE A MORGAN
• 金额: $ 37.63万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-05 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7299684
• 关键词: Ablation; Adult; Alleles; Behavior; Biological Assay; Biological Models; Biology; Candidate Disease Gene; Cells; Cellular biology; Cutaneous; Dermal; Development; Embryo; Epithelial; Epithelium; Experimental Models; Gene Expression; Genes; Genome; Goals; Growth; Hair; Hair follicle structure; Hair shaft structure; In Vitro; Knock-in Mouse; Mediating; Mesenchymal; Methods; Molecular Genetics; Molecular Profiling; Morphogenesis; Mouse Strains; Natural regeneration; Nature; Organ; Organogenesis; Pathway interactions; Population; Property; Reagent; Role; Screening procedure; Signal Pathway; Signal Transduction; Skin; Sorting - Cell Movement; Source; Staging; Stem cells; System; Techniques; Testing; Therapeutic; Thinking; Tissue Engineering; Transgenic Organisms; Validation; Work; appendage; cohort; comparative; direct application; gene function; in vitro Assay; in vivo; insight; keratinocyte; novel; novel strategies; organ regeneration; progenitor; recombinase; reconstitution; tongue papilla

DESCRIPTION (provided by applicant): The hair follicle is a mini-organ that is regenerated from stem cells in the adult. Significant progress has been made in defining and studying the stem cells of the follicular epithelium that regenerate the follicle. However their activation and the differentiation of their progeny to regenerate hair follicles is guided by a specialized mesenchymal population, the dermal papilla (DP). While the importance of these DP cells in follicle formation is clearly established, the nature of the signals generated by them and the ways in which they may change to guide keratinocytes through the successive tasks required to rebuild a follicle and elaborate a hair shaft remain poorly understood. This is in part because the techniques to purify DP cells and manipulate gene expression in them have lagged behind those used to study the epithelial components of the follicle. We have developed novel approaches that allow the purification in bulk of both DP cells and their immediate precursors in development. We have also developed assays to evaluate the inductive activity of these cells during follicle neogenesis. Finally we have developed methods to manipulate gene expression specifically in dermal papilla cells in the context of intact follicles. We will employ these novel reagents and techniques to identify the changes in gene expression that characterize the dermal papilla at different stages in follicle formation, regeneration, and degeneration. The function of these genes in follicle formation and cycling will be tested both in vivo and in vitro. The results of this work will have direct implications for the management of hair growth, regeneration and loss, and also for the management of severe skin wounds where the ability to regenerate cutaneous appendages remains an elusive goal. They will also have broader impact in the fields of stem cell biology and tissue engineering, not only because the hair follicle serves as an important model system in these fields, but because DP are a source of SKPs, an adult derived progenitor population that holds therapeutic promise.

描述（由申请人提供）：毛囊是一种从成年干细胞再生的迷你器官。在定义和研究卵泡再生卵泡上皮的干细胞方面取得了重大进展。但是，它们的激活和后代对再生毛囊的分化是由专门的间充质种群（DP）引导的。尽管这些DP细胞在卵泡形成中的重要性是清楚地确定的，但它们产生的信号的性质以及它们可能通过重建卵泡并阐述脱发所需的连续任务来指导角质形成细胞的方式仍然不足。这部分是因为净化DP细胞和操纵基因表达的技术落后于用于研究卵泡的上皮成分的技术。我们开发了新的方法，可以在大部分DP细胞及其发育中的直接前体中进行纯化。我们还开发了测定方法来评估卵泡新生成期间这些细胞的电感活性。最后，我们开发了在完整卵泡的背景下在皮肤乳头细胞中专门操纵基因表达的方法。我们将采用这些新型试剂和技术来确定基因表达的变化，这些变化在卵泡形成，再生和变性的不同阶段表征了皮肤乳头状。这些基因在卵泡形成和循环中的功能将在体内和体外进行测试。这项工作的结果将对头发生长，再生和损失的管理以及严重皮肤伤口的治疗具有直接影响，在这种情况下，再生皮肤附属物的能力仍然是一个难以捉摸的目标。它们还将在干细胞生物学和组织工程领域产生更大的影响，这不仅是因为毛囊在这些领域充当重要的模型系统，而且因为DP是SKP的来源，SKP是一种成人衍生的祖先种群，具有治疗前景。