Hair Follicle Neogenesis in Response to Wounding

描述(申请人提供)：这个项目的长期目标是更好地了解成年人受伤后的皮肤再生。我们发现，在一只成年小鼠的背部皮肤上受到全层创伤后，毛囊重新形成。这些新的毛囊重新建立干细胞的利基，产生毛发，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，发生在伤口闭合和再上皮化几天后。抑制WNT可阻止毛囊新生，而WNT过表达可促进毛囊的形成。这项资助的主要目标是进一步描述毛囊新生的特征，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，具有再生表皮附属物结构的能力，如毛囊和皮脂腺，并且这种再生可以通过操纵已知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，以及移植到免疫缺陷小鼠身上的人皮肤是否发生新生。我们还将确定成人干细胞群体在皮肤中促进毛囊新生的能力所起的作用。最后，我们将研究已知的毛囊发育所必需的生长因子在毛囊新生中的作用。我们将使用全球基因表达模式来辅助我们的分析和努力，以辨别新生所需的分子途径，以便我们最终能够操纵这些途径来促进伤口愈合。我们将使用转基因和基因敲除小鼠技术来评估毛囊再生所需的念珠酸基因的功能。我们的研究结果应该对了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病的方法具有重要意义。

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.