Core F: Induced Pluripotent Stem Cell Core

核心F：诱导多能干细胞核心 项目摘要/摘要 全基因组关联研究已经确定了近30个与糖尿病风险改变相关的基因。 发展为晚发性阿尔茨海默病(AD)。然而，这些基因究竟是如何影响人类功能的 促进或预防AD的发生或进展的细胞仍不清楚。一 一种很有希望的方法越来越多地被用来检验这类问题，其中包括使用归纳 多能干细胞(IPSCs)，可从对照组和AD患者中产生，然后分化 进入阿尔茨海默病相关的关键脑细胞。2013年，UCI阿尔茨海默病研究中心(ADRC) 成为首个建立诱导多能干细胞(IPSC)核心的ADRC。从那时起，核心已经 生成并向世界各地的研究人员提供AD、MCI和对照受试者的IPSC线路 正在使用这些品系来检查AD基因对人类细胞功能的影响。在本申请中， IPSC Core将继续拥抱AD遗传学和CRISPR基因编辑方面的新进展，以产生 并从UCI的三个ADRC队列(UDS、DS和90+)中分发额外的高度独特的IPSC系列。 通过五个具体目标，IPSC核心将与世界各地的AD研究人员合作(目标1-5)，雇用 创新的基因研究和基因组工程，以促进晚期遗传性AD风险因素的研究 启动AD和专门的AD人群(目标1、3、4)，并教育研究和非专业社区 AD IPSCs的科学应用和影响(目标5)。

Core F: Induced Pluripotent Stem Cell Core Project Summary/Abstract Genome wide association studies have identified almost 30 genes that are associated with altered risk of developing late-onset Alzheimer's disease (AD). Yet, precisely how those genes impact the function of human cells to either promote or protect against the development or progression of AD remains unclear. One promising approach that is increasingly being used to examine such questions involves the use of induced pluripotent stem cells (iPSCs), which can be generated from control and AD subjects and then differentiated into the key brain cells implicated in AD. In 2013, the UCI Alzheimer's disease research center (ADRC) became the first ADRC to establish an induced Pluripotent Stem Cell (iPSC) Core. Since then, the core has generated and provided iPSC lines from AD, MCI and control subjects to researchers around the world who are using these lines to examine the impact of AD genes on human cellular function. In the current application, the iPSC Core will continue to embrace new advances in AD genetics and CRISPR gene editing to generate and distribute additional highly unique iPSC lines from UCI's three ADRC cohorts (UDS, DS, and 90+). Through five specific aims, the iPSC Core will collaborate with AD researchers worldwide (Aims 1-5), employ innovative genetic studies and genome engineering to facilitate the study of genetic AD risk factors in late- onset AD and specialized AD populations (Aims 1, 3, 4), and educate the research and lay communities about the scientific applications and implications of AD iPSCs (Aim 5).