3D Multiscale Reference Atlas for Human Skin

拟议的人类皮肤3D多尺度参考图谱的科学重点是开发第一个 一套全面的、三维的、跨年龄、性别 种族和皮肤位置。皮肤是人体最大的器官，是人体与外界之间的重要屏障。 环境和内部组织，但没有全面的地图存在的三维结构，这 在细胞水平上的器官，也没有一个全面的分子特征图定义这种架构 在整个身体和整个生命周期中。在这里，我们将整合我们最近开发的机器学习指导 具有单细胞和空间多组学分析以产生高含量参考的图像分析系统CODA 地图集成的皮肤图谱将允许研究人员在其整个三维空间中询问皮肤 结构，和/或集中于单个结构，例如脉管系统或毛囊，或单个细胞。我们 将覆盖基因型和表型状态，例如，检查 衰老细胞和干细胞，或细胞外基质（ECM）含量之间的相关性和多样性 真皮成纤维细胞。因为我们将包括多样化和往往代表性不足的人群，我们的多尺度 Atlas还将提供更广泛的皮肤生物学视角，填补关键的缺失信息。最后，通过观察 在整个生命周期中，图集将提供皮肤随年龄变化的结构、细胞和分子变化的视图， 为这个关键器官建立正常生物学的自然史。除了它的原生值之外， 了解皮肤本身，我们预计我们的皮肤图谱将是一个强大的假设生成工具， 生物学家研究了许多问题，皮肤是一个理想的模型系统-稳态更新，修复， 衰老、老化和病原体反应。

The scientific focus of the proposed 3D Multiscale Reference Atlas for Human Skin is to develop the first comprehensive, three-dimensional set of integrated cellular and molecular maps of human skin across age, sex, race and skin location. Skin is the largest human organ, serving as a critical barrier between the external environment and internal tissues, yet no comprehensive map exists for the three-dimensional architecture of this organ at a cellular level, nor is there a comprehensive map of the molecular signatures defining this architecture across the body and across lifespan. Here, we will integrate our recently developed machine learning-guided image analysis system CODA with single-cell and spatial multi-omic analyses to produce high-content reference maps. The integrated Skin Atlas will allow researchers to interrogate the skin in its entire three-dimensional architecture, and/or focus on individual structures such as the vasculature or hair follicles, or individual cells. We will overlay genotypic and phenotypic states to enable, for example, examination of the overlap between senescent cells and stem cells, or the correlation between extracellular matrix (ECM) content and the diversity of dermal fibroblasts. Because we will include diverse and often underrepresented populations, our Multiscale Atlas will also provide a broader view of skin biology, filling in critical missing information. Finally, by looking across lifespan, the Atlas will provide a view of architectural, cellular, and molecular alterations in skin with age, establishing the natural history of normal biology for this critical organ. In addition to its native value for understanding skin itself, we anticipate that our Skin Atlas will be a powerful hypothesis generating tool for biologists studying the many questions for which skin is an ideal model system – homeostatic renewal, repair, senescence, aging, and pathogen response.