Core F: Induced Pluripotent Stem Cell Core

核心F：诱导多能干细胞核心

基本信息

批准号：
9922105
负责人：
Mathew Mark Blurton-Jones
金额：
$ 27.46万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
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/9922105
关键词：
Aged, 80 and over Aging Alzheimer&apos s Disease Alzheimer&apos 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 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 Presenile Alzheimer Dementia Quantitative Trait Loci Research Research Personnel Resources Risk Risk Factors Sampling Single Nucleotide Polymorphism Skin 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 named group neuropathology next generation novel therapeutic intervention outreach polygenic risk score protein expression recruit repository resilience risk variant tau Proteins

项目摘要

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概要/摘要全基因组关联研究已鉴定出近 30 个与罹患癌症风险改变相关的基因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预防 AD 发生或进展的作用仍不清楚。一越来越多地用于研究此类问题的有前途的方法涉及使用诱导多能干细胞 (iPSC)，可以从对照和 AD 受试者中产生，然后进行分化进入与 AD 相关的关键脑细胞。 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。从此以后，核心生成并向世界各地的研究人员提供来自 AD、MCI 和对照受试者的 iPSC 细胞系正在使用这些细胞系来检查 AD 基因对人类细胞功能的影响。在当前的应用中， iPSC 核心将继续拥抱 AD 遗传学和 CRISPR 基因编辑的新进展，以生成并分发来自 UCI 的三个 ADRC 队列（UDS、DS 和 90+）的其他高度独特的 iPSC 系。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 AD 遗传风险因素的研究发病 AD 和特殊 AD 人群（目标 1、3、4），并对研究人员和非专业社区进行相关教育 AD iPSC 的科学应用和影响（目标 5）。