Inductive properties of the dermal papilla of the hair follicle

描述（由申请人提供）：毛囊是由成人干细胞再生的微型器官。在卵泡上皮再生干细胞的定义和研究方面取得了重大进展。然而，它们的激活和后代分化到再生毛囊是由一个专门的间充质群体，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确立，但它们产生的信号的性质以及它们可能改变的方式，以指导角化细胞完成重建毛囊和精心制作毛干所需的连续任务，仍然知之甚少。这在一定程度上是因为纯化DP细胞和操纵其基因表达的技术落后于用于研究卵泡上皮成分的技术。我们已经开发了新的方法，允许大量纯化DP细胞及其在发展中的直接前体。我们还开发了一些方法来评估这些细胞在卵泡新生过程中的诱导活性。最后，我们开发了在完整毛囊的情况下，在真皮乳头细胞中特异性操纵基因表达的方法。我们将使用这些新的试剂和技术来鉴定在毛囊形成、再生和退化的不同阶段真皮乳头特征的基因表达变化。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管理产生直接影响，其中皮肤附属物再生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SKPs的来源，SKPs是一种具有治疗前景的成人衍生祖群体。

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.