Human iPSC Models Core

人类 iPSC 模型核心

• 批准号: 10407940
• 负责人: Celeste Marie Karch
• 金额: $ 67.1万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10407940
• 关键词: 3-Dimensional; Address; Affect; African American; Aging; Alzheimer' s Disease; Apolipoprotein E; Astrocytes; Biochemical; Bioinformatics; Biological Models; Biology; Biometry; Blood Vessels; Brain; CRISPR/Cas technology; Cell physiology; Cells; Cerebrum; Collaborations; Collection; Communities; Complement; Culture Media; Data; Dermal; Disease; Ethnic Origin; Ethnic group; Event; Fibroblasts; Gene Expression; Genome engineering; Genotype; Goals; Hispanic; Human; Individual; Induced pluripotent stem cell derived neurons; Institution; Knowledge; Laboratories; Lipoproteins; Microglia; Modeling; Molecular; Multiomic Data; Mutation; Neurons; Nucleosome Core Particle; Organoids; Outcome; Participant; Pathogenicity; Pathologic; Patients; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Property; Protein Isoforms; Proteomics; Protocols documentation; Research; Resources; Series; Site; Somatic Cell; Source; Structural Biochemistry; Structural Models; Synapses; TREM2 gene; Techniques; Technology; Testing; Training; Work; biobank; brain cell; cell type; cerebrovascular; cohort; data management; engineered stem cells; genotypic sex; human stem cells; induced pluripotent stem cell; lipidomics; metabolomics; multiple omics; neuroinflammation; particle; stem cell model; stem cells; transcriptomics

PROJECT SUMMARY (APOE U19 Core E: Human iPSC Models Core) Human somatic and stem cell models have emerged as a powerful system for modeling the complexities of pathological gene expression, particularly in the early phase of disease. Further, human stem cells can be differentiated into cell-types that secrete apoE and that are affected in disease, such as neurons, astrocytes, microglia, and vascular mural cells (VMCs), as well as 3D “mini-brain” cerebral organoids. The Core E will build upon the existing resources and technology from three institutions at the forefront of stem cell modeling of apoE-related biology and pathobiology in AD: MCJ (Guojun Bu), WUSTL (Celeste Karch), and ISMMS (Julia TCW) to generate a comprehensive collection of well-characterized human iPSC lines with different APOE genotypes from deeply phenotyped patients and through isogenic conversions. The established iPSC lines with different APOE genotypes, sex, ethnicity, and disease status will serve both this U19 and the broader scientific community to address critical gaps in our knowledge of the effects of apoE isoforms in different human brain cell types. In so doing, Core E will support U19 Projects and the broader scientific community by testing a critical component of the ApoE Cascade Hypothesis (ACH): to understand the effects of apoE isoforms on biochemical and cellular events leading to eventual phenotypic outcomes. Thus, Core E will work synergistically with Core A, B, F, G and Projects 1-5 to address the ACH hypothesis and to become an invaluable resource for the broader scientific community.

项目摘要（APOE U19 Core E：人类 iPSC 模型核心） 人类体细胞和干细胞模型已经成为一个强大的系统，用于模拟复杂的生物体 病理基因表达，特别是在疾病的早期阶段。此外，人类干细胞可以 分化为分泌 apoE 并受疾病影响的细胞类型，例如神经元、星形胶质细胞、 小胶质细胞、血管壁细胞 (VMC) 以及 3D“迷你大脑”大脑类器官。核心E将 以干细胞建模前沿的三个机构的现有资源和技术为基础 AD 中 apoE 相关生物学和病理学：MCJ (Guojun Bu)、WUSTL (Celeste Karch) 和 ISMMS (Julia) TCW）生成具有不同 APOE 的全面表征的人类 iPSC 系 来自深度表型患者的基因型和通过等基因转换。已建立的 iPSC 系 具有不同 APOE 基因型、性别、种族和疾病状况的数据将为 U19 和更广泛的人群服务 科学界致力于解决我们对 apoE 异构体在不同疾病中的影响的认识中的关键差距 人类脑细胞类型。通过这样做，Core E 将通过以下方式支持 U19 项目和更广泛的科学界： 测试 ApoE 级联假说 (ACH) 的一个关键组成部分：了解 ApoE 的影响 生化和细胞事件的亚型导致最终的表型结果。因此，Core E 可以工作 与核心 A、B、F、G 和项目 1-5 协同作用，解决 ACH 假设并成为 对于更广泛的科学界来说是宝贵的资源。