Core F: Induced Pluripotent Stem Cell Core

核心F：诱导多能干细胞核心

• 批准号: 10378032
• 负责人: Mathew Mark Blurton-Jones
• 金额: $ 23.43万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378032
• 关键词: Aged, 80 and over; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Award; Biological; Biological Markers; California; Cell Line; Cell physiology; Cells; Cellular biology; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Cognitive; Collaborations; Communities; Consent; Controlled Study; Data; Data Set; Dementia; Development; Differentiation and Growth; Down Syndrome; Early Onset Alzheimer Disease; Ethics; Exhibits; Fibroblasts; Foundations; Funding; Generations; Genes; Genetic; Genetic Diseases; Genetic Risk; Genetic study; Genome engineering; Genotype; Goals; Grant; Human; Impairment; Late Onset Alzheimer Disease; Link; Longevity; Mosaicism; Mutation; Neurochip; PLCG2 gene; Participant; Pathologic; Pathology; Peripheral Blood Mononuclear Cell; Population; Postdoctoral Fellow; Quantitative Trait Loci; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Single Nucleotide Polymorphism; Skin; Special Population; Stem Cell Research; Students; System; TREM2 gene; Teacher Professional Development; Training; Training and Education; United States; United States National Institutes of Health; Universities; Untranslated RNA; Variant; Work; base; brain cell; clinical biomarkers; cohort; cost; data management; education research; gene correction; genome wide association study; induced pluripotent stem cell; innovation; mRNA Expression; neuropathology; next generation; novel therapeutic intervention; outreach; polygenic risk score; protein expression; recruit; repository; resilience; risk variant; stem cell growth; tau Proteins

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).

核心F：诱导多能干细胞核心 项目总结/摘要 全基因组关联研究已经确定了近30个基因与改变的风险有关， 发展为迟发性阿尔茨海默病（AD）。然而，这些基因究竟如何影响人类的功能， 细胞促进或保护AD的发展或进展仍然不清楚。一 一种越来越多地被用来研究这些问题的有前途的方法涉及使用诱导的 多能干细胞（iPSC），其可以从对照和AD受试者产生，然后分化 与AD有关的关键脑细胞2013年，UCI阿尔茨海默病研究中心（ADRC） 成为第一个建立诱导多能干细胞（iPSC）核心的ADRC。从那时起，核心 从AD、MCI和对照受试者中产生并提供iPSC细胞系给世界各地的研究人员， 正在使用这些细胞系来研究AD基因对人类细胞功能的影响。在当前应用中， iPSC Core将继续采用AD遗传学和CRISPR基因编辑的新进展， 并从UCI的三个ADRC队列（UDS，DS和90+）中分配额外的高度独特的iPSC系。 通过五个具体目标，iPSC核心将与全球AD研究人员合作（目标1-5）， 创新的遗传学研究和基因组工程，以促进晚期遗传性AD风险因素的研究， 发病AD和专门AD人群（目标1，3，4），并教育研究和非专业社区， AD iPSC的科学应用和影响（目标5）。