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.

项目摘要 该计划项目的目标是了解蜂窝感应的原因和后果 与年龄相关的神经退行性的驱动器，确定感觉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 疾病和相关痴呆症（ADRD）诱导多能干细胞（IPSC）/Organoid核心，由DRS领导。 Ellerby和Tracy将提供生成IPSC衍生的神经元，星形胶质细胞，小胶质细胞，共培养的专业知识 和脑器官可以理解细胞感应是与年龄相关的神经变性的驱动因素。会 为所有三个项目提供IPSC蜂窝模型的套件，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基本基础架构，培训和支持 参加PPG。此外，它将提供培养，进行电生理所需的一切 记录和图像单元。核心主管在所有这些细胞操作中都有经验，将 批准所有阿尔茨海默氏症相关疾病（ARD）和控制设施的IPSC模型，包括现场和冷冻 来自商业和学术资源的细胞培养物，以确保可重复性，身份验证，测试 支原体和其他单元线维护和验证任务。这些核心主管将批准所有 阿尔茨海默氏病与该设施相关的IPSC模型，包括来自现场和冷冻细胞培养物 商业和学术来源，以确保可重复性，身份验证，对支原体的测试以及其他 单元线维护和验证任务。核心将培训学生和博士后研究员和海外 任何涉及IPSC的研究都需要ESCRO批准，道德培训和MTA。完成这些 描述了目标，“ ADRD IPSC/Organoid Core”的五个具体目标。这些目标是在组织的 需要解决三个项目中描述的研究问题所需的细胞类型或技术 一种有效，优化的方法。该核心的具体目的是：特定目标1 - 生成一批 IPSC从指示的模型得出；特定目标2 - 小胶质细胞。从IPSC中生成小胶质细胞 来自模型（项目1、2和3）；特定目标3 - 星形胶质细胞。从衍生自IPSC的星形胶质细胞产生 模型（项目1和3）；特定目标4 - 皮质神经元。产生皮质神经元（兴奋性和 来自源自模型的IPSC的抑制（项目1、2和3）；特定的目标5 - 脑器官和 共同文化。提供大脑器官（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中为项目1、2和3执行电生理记录 型号。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细胞感应中的相互作用，并确定与AD作战的新途径和目标 和相关的痴呆症。