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Development of a validated human iPSCs-derived microglia and brain organoid co-culture platform to investigate neuro-immune interactions

开发经过验证的人类 iPSC 衍生的小胶质细胞和脑类器官共培养平台，以研究神经免疫相互作用

基本信息

批准号：
2884867
负责人：
金额：
--
依托单位：
University of Aberdeen
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2884867
关键词：
Development validated human iPSCs derived

项目摘要

The overarching goal of this project is to develop a validated human microglia and cortical brain organoid co-culture platform to investigate neuro-immune interactions. Human brain organoids are 3D self-assembled structures of brain cells derived from human pluripotent stem cells (hPSCs) that are grown in a dish. Brain organoids mimic key aspects of human brain development, which makes them an excellent model system for studying human-specific aspects of brain development and neurological disorders. However, brain organoids innately generate only ectodermal-originated brain cells not cells from other lineages such as microglia. Microglia are resident immune cells in the brain comprising about 5-10% of total cells in the human brain and play important roles in brain development, homeostasis, and neuroinflammation during pathological conditions. Therefore, establishing a platform for hPSC-derived microglia integrated into 3D human brain organoids provides unique opportunities to study human microglia and to model brain disorders. Previous studies that have shown the feasibility of generating microglia-containing organoids failed to validate the system. In this project, we aim to optimize hPSC-derived microglia and brain organoid co-culture method by systematic comparisons of different conditions and novel approaches and validate the platform by comparing it with fresh human embryonic tissue at the cellular, transcriptomic, and functional levels. Furthermore, we will develop a pipeline for bioinformatic analyses of neuron-immune interactions from transcriptomic data.

该项目的总体目标是开发一个有效的人类小胶质细胞和皮质脑类器官共培养平台，以研究神经免疫相互作用。人脑类器官是在培养皿中培养的人类多能干细胞（hPSCs）衍生的脑细胞的三维自组装结构。脑类器官模仿人类大脑发育的关键方面，这使它们成为研究人类大脑发育和神经疾病的特定方面的优秀模型系统。然而，脑类器官天生只产生外胚层起源的脑细胞，而不是来自其他谱系的细胞，如小胶质细胞。小胶质细胞是大脑中的常驻免疫细胞，约占人脑总细胞的5-10%，在大脑发育、体内平衡和病理状态下的神经炎症中起重要作用。因此，建立一个将hpsc衍生的小胶质细胞整合到三维人脑类器官的平台，为研究人类小胶质细胞和模拟大脑疾病提供了独特的机会。先前的研究表明，产生含有小胶质细胞的类器官的可行性未能验证该系统。在本项目中，我们旨在通过系统比较不同条件和新方法来优化hpsc衍生的小胶质细胞和脑类器官共培养方法，并通过将其与新鲜人胚胎组织进行细胞、转录组和功能水平的比较来验证该平台。此外，我们将从转录组学数据中开发神经免疫相互作用的生物信息学分析管道。