Inductive properties of the dermal papilla of the hair follicle

毛囊真皮乳头的感应特性

• 批准号: 7480260
• 负责人: BRUCE A MORGAN
• 金额: $ 36.87万
• 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/7480260
• 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（申请人提供）：毛囊是由成人干细胞再生的微型器官。在定义和研究再生毛囊的毛囊上皮干细胞方面已经取得了重大进展。然而，它们的激活及其子代分化以再生毛囊是由特殊的间充质群体——真皮乳头（DP）引导的。虽然这些 DP 细胞在毛囊形成中的重要性已经明确，但它们产生的信号的性质以及它们可能改变以引导角质形成细胞完成重建毛囊和细化毛干所需的连续任务的方式仍然知之甚少。部分原因是纯化 DP 细胞和操纵其中基因表达的技术落后于用于研究卵泡上皮成分的技术。我们开发了新的方法，可以批量纯化 DP 细胞及其正在发育的直接前体细胞。我们还开发了评估这些细胞在卵泡新生过程中的诱导活性的测定方法。最后，我们开发了在完整毛囊背景下专门操纵真皮乳头细胞中基因表达的方法。我们将采用这些新颖的试剂和技术来识别基因表达的变化，这些变化是真皮乳头在毛囊形成、再生和退化的不同阶段的特征。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毛发生长、再生和脱落的治疗以及严重皮肤伤口的治疗产生直接影响，在这些伤口中，皮肤附属器再生的能力仍然是一个难以实现的目标。它们还将在干细胞生物学和组织工程领域产生更广泛的影响，不仅因为毛囊是这些领域的重要模型系统，而且因为 DP 是 SKP 的来源，SKP 是一种具有治疗前景的成人祖细胞群。