Hair Follicle Neogenesis in Response to Wounding

描述（由申请人提供）：该项目的长期目标是更好地了解成人受伤后的皮肤再生。我们发现，在成年老鼠的背部皮肤上全层伤口后，毛囊会重新形成。这些新的毛囊重新建立它们的干细胞生态位，产生头发，并进行循环。这种再生在形态和分子上类似于胚胎毛囊的发育，发生在伤口愈合和再上皮化后几天。抑制wnt可阻止毛囊新生，而过表达wnt可促进毛囊形成。这项资助的主要目标是进一步表征毛囊新生，并了解控制这一现象的分子信号。我们假设，成年哺乳动物，包括人类，具有再生表皮附件结构的能力，如毛囊和皮脂腺，这种再生可以通过操纵已知的对毛囊发育重要的途径来增强或抑制。我们的目的是研究衰老、毛发周期、新生所需的最小刺激的影响，以及移植到免疫缺陷小鼠的人皮肤是否发生新生。我们还将确定成体干细胞群体在皮肤中的作用，因为它们有能力促进毛囊新生。最后，我们将研究已知的毛囊发育所需的生长因子在毛囊新生中的作用。我们将使用全局基因表达模式来协助我们的分析和努力，以辨别新生所需的分子途径，以便我们最终可以操纵这些途径来改善伤口愈合。我们将使用转基因和敲除小鼠技术来评估毛囊再生所需的候选基因的功能。我们的研究结果应该对理解皮肤生物学和开发未来治疗伤口、脱发和其他退行性皮肤疾病具有重要意义。

DESCRIPTION (provided by applicant): The long-term goal of this project is to better understand skin regeneration following wounding in adults. We discovered that after a full thickness wound on the back skin of an adult mouse, hair follicles form de novo. These new follicles reestablish their stem cell niche, produce hair, and cycle. This regeneration resembles embryonic hair follicle development morphologically and molecularly, and occurs several days after wound closure and reepithelialization. Inhibition of wnt prevents hair follicle neogenesis, while wnt overexpression enhances hair follicle formation. The major goal of this grant is to further characterize hair follicle neogenesis and understand the molecular signals controlling this phenomenon. We hypothesize that adult mammals, including humans, have the capacity to regenerate epidermal adnexal structures, such as hair follicles and sebaceous glands, and that this regeneration can be enhanced or inhibited by manipulating pathways known to be important for hair follicle development. Our aims are to study the effects of aging, hair cycle, minimum stimulus required for neogenesis, and whether neogenesis occurs in human skin grafted to immunodeficint mice. We will also define the role of adult stem cell populations in the skin for their ability to contribute to hair follicle neogenesis. Lastly, we will examine the role of growth factors known to be necessary for hair follicle development in follilce neogenesis. We will use global gene expression patterns to assist with our analysis and effort to discern the molecular pathways necessary for neogenesis so that we can eventually manipulate these pathways to improve wound healing. We will use transgenic and knockout mouse technology to evaluate the function of candiadate genes necessary for hair follicle regeneration. Our results should have major implications for understanding skin biology and developing future treatments for wounds, alopecia and other degenerative skin disorders.