Inductive properties of the dermal papilla of the hair follicle

描述（由申请人提供）：毛囊是一种由成人干细胞再生的微型器官。在定义和研究再生卵泡的卵泡上皮干细胞方面已经取得了重大进展。然而，它们的活化和其后代的分化以再生毛囊是由专门的间充质群体（毛乳头（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精心制作毛干所需的连续任务的方式仍然知之甚少。这部分是因为纯化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，允许在批量的DP细胞和他们的直接前体的发展中的纯化。我们还开发了检测方法来评估这些细胞在卵泡新生过程中的诱导活性。最后，我们已经开发出的方法来操纵基因表达，特别是在毛乳头细胞的背景下，完整的毛囊。我们将采用这些新的试剂和技术，以确定在毛囊形成，再生和退化的不同阶段的特征毛乳头的基因表达的变化。这些基因在卵泡形成和周期中的功能将在体内和体外进行测试。这项工作的结果将直接影响头发生长，再生和损失的管理，也为管理严重的皮肤伤口，再生皮肤附属物的能力仍然是一个难以捉摸的目标。它们也将在干细胞生物学和组织工程领域产生更广泛的影响，不仅因为毛囊在这些领域中作为重要的模型系统，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细胞群体。

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.