Organ Specific Project

摘要，机关具体项目 人体皮肤及其附属物是人体最大的器官。除了其屏障功能外， 皮肤参与与维持体内平衡控制相关的任务，如温度调节、维持 机械结构的完整性和韧性，并作为免疫和其他类型的细胞的储存库 对防御和伤口修复至关重要。机械论研究表明，这些有害的变化 功能源于内在因素和外在因素的结合。这些因素会受到以下因素的影响 年龄、性别和种族。随着人类年龄的增长，几乎所有的皮肤功能都会受到影响。这些问题包括结构方面的损失 正直和韧性，自我更新能力受损，伤口修复和疤痕形成差，温度低 调节汗腺分泌不足，荷尔蒙分泌减少，色素沉着受损 易受环境破坏，并增加炎症和衰老。这些变化导致 皮肤脆弱和疾病，表明越来越需要加强对皮肤的了解 微环境及其与年龄、性别和种族相关的变化。除了年龄、性别和种族- 与ECM结构相关的机械结构变化，即皮肤内的细胞生态系统 在整个生命周期内会发生显著变化。在3D皮肤微环境中，ECM架构、细胞- 细胞外基质相互作用，细胞类型/亚群的丰富性，其潜在的分子活性/功能基因 表达模式，以及不同身体部位的异质性还知之甚少。我们建议有六个 旨在绘制正常的、未患病的皮肤作为年龄、种族、性别和身体位置的函数。 该项目的前两个目标将制作皮肤的3D参考建筑地图，作为 年龄、性别、种族和皮肤位置，而接下来的三个目标将产生相关的3D参考细胞地图。 建筑制图(目标1-2)将评估三维分子组成和形态/拓扑 皮肤的主要多细胞结构，包括表皮、真皮、毛囊、顶分泌腺和小汗腺， 血管和神经。AIMS 1-2还将测量皮肤细胞外基质的形态和排列程度 在3D中。细胞测绘(目标3-5)将产生详尽的空间分辨的细胞和分子轮廓 毛囊、表皮和真皮，以及大体积3D“免疫细胞图”、“基质细胞图”和 整个皮肤的“干细胞图谱”。高内容集成(AIM 6)将产生一个用户友好的软件， 为非专业人员提供查询与上下文相关的参考地图的能力，将两者集成 建筑和蜂窝隔间。

Summary, Organ Specific Project Human skin and its appendages comprise the largest organ in the body. In addition to its barrier function, the skin is involved in tasks related to maintaining homeostatic control such as temperature regulation, maintaining mechano-structural integrity and resilience, and serving as a reservoir for immune and other cell types that are critical for defense and wound repair. Mechanistic studies have shown that deleterious changes to these functions stem from combinations of both intrinsic and extrinsic factors. These factors are then influenced by age, sex, and race. As humans age, nearly all skin functions are affected. These include the loss of structural integrity and resilience, impaired self-renewal capabilities, poor wound repair and scarring, poor temperature regulation from deficiencies in eccrine sweat glands, decreased hormone production, impaired pigmentation and susceptibility to environmental damage, and increased inflammation and senescence. These changes lead to skin fragility and disease, pointing to the increased need for enhanced understanding of the skin microenvironment and its age-, sex-, and race-associated changes. In addition to the age-, sex-, and race- associated mechano-structural changes to the architecture of the ECM, the cellular ecosystem within the skin changes significantly over the lifespan. Within the 3D skin microenvironment, changes in ECM architecture, cell- ECM interactions, abundance of cell types/subpopulations, their underlying molecular activity/functional gene expression patterns, and heterogeneity across different body locations are poorly understood. We propose six Aims to map the normal, non-diseased skin as a function of age, race, sex, and location on the body. The first two Aims of the Project will produce 3D reference architectural maps of skin as a function of age, sex, race, and skin location, while the next three Aims will produce associated 3D reference cellular maps. Architectural mapping (Aims 1-2) will assess the 3D molecular composition and morphology/topology of the major multi-cellular structures of skin, including epidermis, dermis, hair follicles, apocrine and eccrine glands, blood vessels, and nerves. Aims 1-2 will also measure morphology and degree of alignment of the ECM of skin in 3D. Cellular mapping (Aims 3-5) will produce exhaustive spatially resolved cellular and molecular profiles of hair follicles, epidermis, and dermis, as well as large-volume 3D “immune cell maps”, “stromal cell maps”, and “stem cell maps” of the entire skin. High-content integration (Aim 6) will produce a user-friendly software that provides non-experts with the ability to interrogate context-dependent reference maps integrating both architectural and cellular compartments.