Resource Core B - Modeling of skin disease for mechanistic analysis and therapeutic discovery

摘要-资源核心B 许多技术、物流和成本障碍阻碍了高效和可行的高端实验 皮肤研究中的方法。核心B所做的努力：为皮肤病的机理分析和建模 治疗发现“将系统地克服这些障碍，为皮肤研究人员提供 人类皮肤样本，利用我们在产生和分析复杂的小鼠基因和 人类IPSC衍生的皮肤病模型，并为基因组学提供与Core C的简化界面 和转录分析。与此同时，皮肤生物学和疾病研究的进入门槛将是 通过向初级研究人员和新进入皮肤生物学的研究人员提供试点补助金来降低成本 疾病领域，高端技术的成本将由用户奖学金支付。核心B将提供 用户在高级皮肤研究方面的专业技术、临床和科学知识和服务 关键研究基础设施，通过提供A)临床和组织病理学专业知识，便于检索 正常和患病的人类皮肤，并可获得有效的多路复用皮肤标记分析，用于生理和 皮肤病研究；b)基本皮肤功能的生理学研究的科学专门知识和服务 拥有先进的小鼠遗传模型以及细胞分离和成像技术；以及c)科学专业知识 以及使用患者派生的IPSC技术和基于CRISPR的人类皮肤病建模服务 用于机制分析和治疗靶点发现的基因编辑和表达操纵。这些 具体目标将通过以下方式实现：1)提供我们大量存档的正常和 患病的人类皮肤；2)方便获取未识别的新鲜人类皮肤样本；3)先进的多路复用器 标记蛋白的免疫组织化学成像；4)辅助产生最先进的遗传小鼠 皮肤功能研究模型；5)提供针对特定皮肤细胞的精细分离技术培训 5)为体外和体内先进的活体成像提供培训；6)产生患者IPSCs和 将它们分化为皮肤细胞以模拟人类皮肤病；以及7)研究候选皮肤病基因 通过产生等基因突变和对照IPSC来源的皮肤细胞和通过基于Cas9的基因表达 操纵。

Summary – Resource Core B Many technical, logistical and cost barriers hinder efficient and feasible access to high-end experimental approaches in skin research. Efforts by Core B, “Modeling of skin disease for mechanistic analysis and therapeutic discovery” will systematically overcome these barriers for skin researchers by facilitating access to human skin samples, harnessing our expertise in generating and analyzing sophisticated mouse genetic and human iPSC-derived models of skin disease, and providing a streamlined interface with Core C for genomics and transcriptional analyses. In parallel, the entry barriers to skin biology and diseases research will be lowered by providing Pilot Grants to junior investigators and researchers newly entering the skin biology and diseases field, and the costs of high-end technologies will be defrayed by User Scholarships. Core B will offer users specialized technical, clinical and scientific know-how and services in advanced skin research as well as critical research infrastructure by providing A) clinical and histopathological expertise for easy retrieval of normal and diseased human skin and access to efficient multiplexed skin marker analysis for physiological and skin disease studies; B) scientific expertise and service for physiological studies of fundamental skin functions with advanced genetic mouse models and cell isolation and imaging technologies; and C) scientific expertise and service for human skin disease modeling with patient-derived iPSC technology and with CRISPR-based gene editing and expression manipulation for mechanistic analysis and therapeutic target discovery. These goals will specifically be achieved by 1) providing samples from our vast collection of archived normal and diseased human skin; 2) facilitating access to de-identified fresh human skin samples; 3) advanced multiplexed immunohistochemical imaging of marker proteins; 4) aiding in the generation of state-of-the-art genetic mouse models for skin functional studies; 5) providing training in refined isolation technologies for specific skin cell populations; 5) providing training for advanced live imaging in vitro and in vivo; 6) generating patient iPSCs and differentiating them to skin cells to model human skin disease; and 7) studying candidate skin disease genes by generating isogenic mutant and control iPSC-derived skin cells and through Cas9-based gene expression manipulation.