Regulation of scar free wound healing in salamanders

项目摘要 严重的皮肤病是最具破坏性的健康状况之一， 治疗困难的挑战。这些都是由遗传疾病和受伤引起的， 例如超过50万名严重烧伤受害者长期遭受的折磨， 仅在美国每年就有100万人住院。今天的顶级治疗，包括主要的 皮肤移植，仍然在努力克服人类皮肤相对 基本修复过程。虽然这些通常会恢复结构完整性，但它们通常 导致广泛的疤痕，不仅导致毁容和伴随 心理创伤，但也严重丧失功能，包括受损 敏感性和感染易感性增加。 更有效的皮肤疗法的发展现在将大大受益于 对自然界所表现出的非凡愈合能力的新认识 再生脊椎动物为此，我们对美西蝾螈的长期研究 蝾螈，这些物种中的冠军，正在识别关键分子， 调节途径和无瘢痕再生的细胞过程。 在这里，我们将这些解决皮肤再生的核心问题， 美西蝾螈的筛选和分析工具。该项目的目的是：1）明确 Sall 4在真皮和表皮中促进无瘢痕皮肤再生的作用。（二） 利用皮肤细胞转录组数据来定义和功能阐明 不同的皮肤细胞群调节无疤痕再生。3)我们将翻译 我们在体外模型中发现了SALL 4在调节蝾螈胶原蛋白中的作用， 并利用这一新知识来尝试促进疤痕- 在人体细胞中的自由创伤愈合。 总之，这些实验将揭示和表征 美西螈对损伤的再生反应和哺乳动物对损伤的非再生反应， 确定前者所需的分子和途径，以评估其潜在的 加强后者。因此，这些研究的最终目的是提高生活质量 治疗慢性开放性伤口和功能失调的疤痕组织

Project Summary Serious skin disorders count among the most devastating health conditions and most difficult treatment challenges. These arise both from genetic diseases and from injuries, such as the often-debilitating long-term suffering of the >500,000 serious burn victims who are hospitalized every year in the US alone. Today's top treatments, including major skin grafts, still struggle to overcome the key natural limitations of human skin's relatively basic repair processes. While these generally restore structural integrity, they often result in extensive scarring that not only causes disfigurement and accompanying psychological trauma, but also significant loss of functionality, including impaired sensitivity and increased susceptibility to infection. The development of more effective skin therapies now stands to benefit greatly from emerging new understanding of the remarkable healing abilities exhibited by naturally regenerative vertebrates. To this end, our longstanding work on the “axolotl” salamander, the champion among such species, is identifying critical molecules, regulatory pathways and cellular processes underlying scar-free regeneration. Here, we will these address central issues in skin regeneration using cutting edge screening and analysis tools in axolotl. The aim of the project is to: 1) define the exact role of Sall4 in the dermis and epidermis for promoting scar free skin regeneration. 2) harness skin cell transcriptome data to define and functionally elucidate the role of different skin cell populations in regulating scar free regeneration. 3) We will translate our findings of the role of SALL4 in regulating collagen in axolotls into an in vitro model of human skin regeneration and use this new knowledge to attempt to promote scar- free wounding healing in human cells. In summary, these experiments will reveal and characterize key differences between the axolotl's regenerative and the mammal's non-regenerative responses to injury, identifying molecules and pathways required for the former to assess their potential for enhancing the latter. The ultimate aim of these studies is thus to improve quality of life for people with chronic open wounds and dysfunctional scar tissue.