ADRD Induced pluripotent stem cell/organoid core

ADRD 诱导多能干细胞/类器官核心

• 批准号: 10647771
• 负责人: Lisa M Ellerby
• 金额: $ 33.98万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647771
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; Astrocytes; Brain; Cell Aging; Cell Communication; Cell Culture Techniques; Cell Line; Cell model; Cells; Cerebrum; Coculture Techniques; Dementia; Disease; Disease Progression; Electrophysiology (science); Ensure; Equipment; Ethics; Freezing; Frontotemporal Dementia; Goals; Human; Image; Induced pluripotent stem cell derived neurons; Infrastructure; Intervention; Knowledge; Maintenance; Measurement; Microglia; Modeling; Mus; Mycoplasma; Neurons; Onset of illness; Organizational Objectives; Organoids; Participant; Pathway interactions; Patients; Postdoctoral Fellow; Quarantine; Reproducibility; Research; Research Personnel; Role; Scientist; Services; Source; Specificity; Technology; Testing; Training; Validation; age related; age related neurodegeneration; cell type; cellular imaging; combat; experience; induced pluripotent stem cell; mouse model; programs; senescence; stem cell model; student training; tau mutation

PROJECT SUMMARY The goals of the Program Project are to understand the causes and consequences of cellular senescence as a driver of age-related neurodegeneration, determine new targets and mechanisms by which senescent cells drive disease, and identify new targets for interventions that alter disease onset and/or progression. The Alzheimer’s disease and related dementias (ADRD) induced pluripotent stem cell (iPSC)/organoid core, led by Drs. Ellerby and Tracy, will provide expertise in generating iPSC-derived neurons, astrocytes, microglia, co-cultures and brain organoids to understand cellular senescence as a driver of age-related neurodegeneration. It will provide a suite of iPSC cellular models to all three projects and validate all the derived cell types, co-cultures and brain organoids. The Core will provide essential infrastructure, training and support for all scientists participating in the PPG. In addition, it will provide everything needed to culture, conduct electrophysiological recordings, and image cells. The Core directors have experience in all of these cell manipulations and will approve all Alzheimer’s-related disease (ARD) and control iPSC models for the facility, including live and frozen cell cultures from commercial and academic sources, to ensure reproducibility, authentication, testing for mycoplasma, and other cell line maintenance and validation tasks. These Core directors will approve all Alzheimer’s disease related and control iPSC models for the facility, including live and frozen cell cultures from commercial and academic sources, to ensure reproducibility, authentication, testing for mycoplasma, and other cell line maintenance and validation tasks. The Core will train students and postdoctoral fellows and oversee any research involving iPSCs that require ESCRO approvals, ethics training and MTAs. To accomplish these goals, five specific aims of the ‘ADRD iPSC/Organoid Core’ are described. These goals are organized around the cell type or technology that is needed to address the research questions described in the three projects in an efficient and optimized approach. The Specific Aims of this Core are: Specific Aim 1 – Generate a bank of iPSCs derived from the indicated models; Specific Aim 2 – Microglia. Generate microglia from iPSCs derived from the models (Projects 1, 2 and 3); Specific Aim 3 – Astrocytes. Generate astrocytes from iPSCs derived from the models (Projects 1 and 3); Specific Aim 4 – Cortical Neurons. Generate cortical neurons (excitatory and inhibitory) from iPSCs derived from the models (Projects 1, 2 and 3); Specific Aim 5 – Cerebral Organoids and Co-cultures. Provide cerebral organoids (Projects 1 and 3); Specific Aim 6 – Electrophysiology and Imaging. We will perform electrophysiological recordings for Projects 1, 2 and 3 in both human cellular models and mouse models. These aims will provide models and technology that will enhance our knowledge of cell type specificity and interactions in AD cellular senescence and identify new pathways and targets of opportunity to combat AD and related dementias.

项目概要 该计划项目的目标是了解细胞衰老的原因和后果 与年龄相关的神经退行性变的驱动因素，确定衰老细胞驱动的新目标和机制 疾病，并确定改变疾病发作和/或进展的干预措施的新目标。 疾病和相关痴呆（ADRD）诱导多能干细胞（iPSC）/类器官核心，由博士领导。 Ellerby 和 Tracy 将提供生成 iPSC 衍生神经元、星形胶质细胞、小胶质细胞、共培养物方面的专业知识 和大脑类器官，以了解细胞衰老是与年龄相关的神经变性的驱动因素。 为所有三个项目提供一套 iPSC 细胞模型，并验证所有衍生细胞类型、共培养 核心将为所有科学家提供必要的基础设施、培训和支持。 此外，它将提供培养、进行电生理检查所需的一切。 核心董事在所有这些细胞操作方面都有经验，并且愿意。 批准该设施的所有阿尔茨海默病相关疾病 (ARD) 和对照 iPSC 模型，包括活体和冷冻模型 来自商业和学术来源的细胞培养物，以确保可重复性、认证、测试 支原体以及其他细胞系维护和验证任务将由这些核心主管批准。 该设施的阿尔茨海默病相关和对照 iPSC 模型，包括来自 商业和学术来源，以确保可重复性、验证、支原体测试和其他 细胞系维护和验证任务将培训学生和博士后研究员并进行监督。 任何涉及 iPSC 的研究都需要 ESCRO 批准、道德培训和 MTA 才能完成这些任务。 目标，描述了“ADRD iPSC/类器官核心”的五个具体目标，这些目标是围绕这些目标组织的。 解决三个项目中描述的研究问题所需的细胞类型或技术 该核心的具体目标是： 一种高效且优化的方法。 具体目标 1 – 生成一组 源自指定模型的 iPSC；具体目标 2 – 从源自 iPSC 生成小胶质细胞。 从模型（项目 1、2 和 3）；具体目标 3 – 从源自 iPSC 生成星形胶质细胞。 模型（项目 1 和 3）；具体目标 4 – 生成皮质神经元（兴奋性神经元和皮质神经元）。 具体目标 5 – 脑类器官和 提供大脑类器官（项目 1 和 3）；具体目标 6 – 电生理学和成像。 我们将在人类细胞模型和小鼠中对项目 1、2 和 3 进行电生理记录 这些目标将提供模型和技术来增强我们对细胞类型特异性的了解。 AD 细胞衰老中的相互作用和相互作用，并确定对抗 AD 的新途径和机会目标 以及相关的痴呆症。