Human iPSC Models Core

项目总结(APOE U19 Core E：Human IPSC Models Core) 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 病理性基因表达，尤其是在疾病的早期阶段。此外，人类干细胞可以 分化为分泌载脂蛋白E并受疾病影响的细胞类型，如神经元、星形胶质细胞、 小胶质细胞、血管壁细胞(VMCs)以及3D“迷你脑”脑器官。核心E将 建立在三个处于干细胞建模前沿的机构的现有资源和技术基础上 阿尔茨海默病的载脂蛋白E相关生物学和病理生物学：MCJ(国军)、WUSTL(塞莱斯特·卡奇)和ISMMS(Julia TCW)，以产生具有不同APOE的、具有良好特性的人类IPSC系的全面集合 来自表型较深的患者和通过等基因转换的基因类型。已建立的IPSC生产线 不同的载脂蛋白E基因型别、性别、种族和疾病状况将服务于这一U19和更广泛的 科学界解决我们对载脂蛋白E亚型在不同环境中的影响的认识上的严重差距 人类脑细胞类型。在此过程中，Core E将通过以下方式支持U19项目和更广泛的科学界 测试载脂蛋白E级联假说(ACH)的一个关键部分：了解载脂蛋白E的影响 生化和细胞事件的异构体导致最终的表型结果。因此，核心E将会工作 与核心A、B、F、G和项目1-5协同解决ACH假设并成为 对于更广泛的科学界来说，这是无价的资源。

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.