ADRD Induced pluripotent stem cell/organoid core

ADRD 诱导多能干细胞/类器官核心

• 批准号: 10491068
• 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/10491068
• 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; 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; Organoids; Participant; Pathway interactions; Patients; Postdoctoral Fellow; Quarantine; Reproducibility; Research; Research Personnel; Role; Scientist; Services; Source; Specificity; Technology; Testing; Training; Training Support; Validation; age related; age related neurodegeneration; cell type; cellular imaging; combat; disorder control; 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。阿尔茨海默氏症 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。它将 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 和大脑类器官。该核心将为所有科学家提供必要的基础设施、培训和支持 参加PPG。此外，它将提供培养、进行电生理学所需的一切 录音和图像单元。核心董事在所有这些细胞操作方面都有经验，并将 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 支原体和其他细胞系维护和验证任务。这些核心董事将批准所有 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。核心将培训学生和博士后研究员并监督 任何涉及 iPSC 且需要 ESCRO 批准、道德培训和 MTA 的研究。为了完成这些 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 解决三个项目中描述的研究问题所需的细胞类型或技术 一种高效且优化的方法。该核心的具体目标是： 具体目标 1 – 生成一组 来自所示模型的 iPSC；具体目标 2 – 小胶质细胞。从衍生的 iPSC 生成小胶质细胞 来自模型（项目 1、2 和 3）；具体目标 3 – 星形胶质细胞。从衍生自 iPSC 中生成星形胶质细胞 模型（项目 1 和 3）；具体目标 4 – 皮质神经元。生成皮质神经元（兴奋性和 抑制性）来自模型衍生的 iPSC（项目 1、2 和 3）；具体目标 5 – 脑类器官和 共培养。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进行项目 1、2 和 3 的电生理记录 模型。这些目标将提供模型和技术，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。