Human iPSC Models Core

人类 iPSC 模型核心

• 批准号: 10667452
• 负责人: Celeste Marie Karch
• 金额: $ 66.58万
• 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/10667452
• 关键词: 3-Dimensional; Address; Affect; African American; Aging; Alzheimer' s Disease; Apolipoprotein E; Astrocytes; Biochemical; Biochemistry; Bioinformatics; Biological Models; Biology; Biometry; Blood Vessels; CRISPR/Cas technology; Cell physiology; Cells; Cerebrum; Collaborations; Collection; Communities; Complement; Culture Media; Data; Dermal; Disease; EIF2B2 gene; Ethnic Origin; Ethnic Population; 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; Reproducibility; Research; Resources; Series; Site; Somatic Cell; Source; Structural Models; Synapses; TREM2 gene; Techniques; Technology; Testing; Training; Work; apolipoprotein E-1; biobank; brain cell; cell type; cerebrovascular; cohort; data management; engineered stem cells; human stem cells; induced pluripotent stem cell; lipidomics; metabolomics; multiple omics; neuroinflammation; particle; sex; 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.

项目总结（APOE U19核心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 病理基因表达，特别是在疾病的早期阶段。此外，人干细胞可以是 分化为分泌apoE并在疾病中受影响的细胞类型，如神经元，星形胶质细胞， 小胶质细胞和血管壁细胞（VMC），以及3D“迷你脑”脑类器官。核心E将 建立在现有的资源和技术，从三个机构在干细胞建模的前沿， AD中apoE相关的生物学和病理学：MCJ（Guojun Bu），WUSTL（塞莱斯特Karch）和ISMMS（Julia TCW）以产生具有不同APOE的充分表征的人iPSC系的综合集合 从深度表型化的患者和通过同基因转换的基因型。已建立的iPSC系 对于不同的APOE基因型，性别、种族和疾病状态将服务于U19和更广泛的研究。 科学界，以解决关键差距，我们的知识的影响，载脂蛋白E亚型在不同的 人类脑细胞类型。通过这样做，核心E将支持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 同种型对生物化学和细胞事件的影响，导致最终的表型结果。因此，核心E将工作 与核心A、B、F、G和项目1-5协同作用，以解决ACH假设，并成为 为广大科学界提供了宝贵的资源。