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.

项目总结 该计划项目的目标是了解细胞衰老的原因和后果 年龄相关神经变性的驱动因素，确定衰老细胞驱动的新靶点和机制 并为改变疾病发生和/或进展的干预措施确定新的目标。阿尔茨海默氏症 疾病和相关痴呆(ADRD)诱导的多能干细胞(IPSC)/类器官核心，由Dr。 Ellerby和Tracy将提供在IPSC来源的神经元、星形胶质细胞、小胶质细胞、共培养 和脑有机体，以了解细胞衰老是年龄相关神经退化的驱动因素。会的 为所有三个项目提供一套IPSC细胞模型，并验证所有派生的细胞类型、共培养 和脑器官。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，它还将提供培养、进行电生理所需的一切 记录和图像单元。核心董事在所有这些单元操作方面都有经验，并将 批准设施的所有阿尔茨海默氏症相关疾病(ARD)和控制IPSC模型，包括活的和冷冻的 来自商业和学术来源的细胞培养，以确保重复性、认证、测试 支原体，以及其他细胞系的维护和验证任务。这些核心董事将批准所有 该设施的阿尔茨海默病相关和控制IPSC模型，包括来自 商业和学术来源，以确保可重复性、身份验证、支原体检测等 细胞线维护和验证任务。该中心将培训学生和博士后研究员，并监督 任何涉及IPSC的研究，需要获得ESCRO批准、道德培训和MTA。要实现这些目标 目标，描述了‘ADRD iPSC/有机核心’的五个具体目标。这些目标是围绕以下内容组织的 中描述的三个项目中描述的研究问题所需的细胞类型或技术 一种高效和优化的方法。这个核心的具体目标是：具体目标1-建立一个银行 IPSCs来源于指定的模型；特异性靶点2-小胶质细胞。从IPSCs来源的细胞中产生小胶质细胞 来自模型(项目1、2和3)；特定目标3-星形胶质细胞。从来源的IPSCs产生星形胶质细胞 模型(方案1和方案3)；特定目标4-皮质神经元。产生皮质神经元(兴奋性和 来自模型的IPSCs(项目1、2和3)；特定目标5-脑有机体和 共同文化。提供脑器官(项目1和3)；特定目标6-电生理学和成像。 我们将在人类细胞模型和小鼠模型中对项目1、2和3进行电生理记录 模特们。这些目标将提供模型和技术，以增强我们对细胞类型特异性的了解 以及AD细胞衰老中的相互作用，并确定抗击AD的新途径和新靶点 以及相关的痴呆症。