Human iPSC Models Core

人类 iPSC 模型核心

基本信息

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
项目类别：
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&apos 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

项目摘要

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核心E：人IPSC模型核心）人类体细胞和干细胞模型已成为一种强大的系统，用于建模病理基因表达，特别是在疾病的早期。此外，人类干细胞可以是分化为秘密apoE和在疾病中受影响的细胞类型，例如神经元，星形胶质细胞，小胶质细胞和血管壁画细胞（VMC），以及3D“迷你脑”大脑器官。核心将基于三个机构的现有资源和技术，位于干细胞建模的最前沿 AD中与APOE相关的生物学和病理学：MCJ（Gujun BU），Wustl（Celeste Karch）和ISMMS（Julia） TCW）与不同的APOE生成全面的特征良好的人IPSC系列来自深层表型患者的基因型以及通过同基因转化。已建立的IPSC线具有不同的APOE基因型，性别，种族和疾病状况将为U19服务和更广泛的服务科学界在我们了解ApoE同工型在不同的不同的知识中解决关键差距人脑细胞类型。这样做，核心E将支持U19项目和更广泛的科学界测试APOE级联假设（ACH）的关键组成部分：了解APOE的影响生化和细胞事件的同工型导致最终表型结果。核心E将起作用与核心A，B，F，G和1-5的项目协同解决ACH假设并成为一个对更广泛的科学界的宝贵资源。