REGIONAL SPECIFICATION OF ASTROCYTE DOMAINS: FROM DEVELOPMENT TO BEHAVIOUR

星形胶质细胞域的区域规范：从发育到行为

• 批准号: RGPIN-2016-06306
• 负责人: Morshead, Cindi
• 金额: $ 2.77万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629357
• 关键词: REGIONAL; SPECIFICATION; ASTROCYTE; DOMAINS; DEVELOPMENT

The human brain is composed of two main cell types: neurons and glia. Both are derived from neural stem cells during development. Astrocytes, one type of glial cells, are the most abundant cells in the brain. Historically, however, astrocytes have been understudied, as they were thought only to serve as support cells for the proper function of the communicating neurons. Astrocytes have since been shown to play a major role in the proper functioning of the brain. Similar to neurons, they are a diverse group of cells, but little is known about how they achieve this diversity and how this relates to brain function. Our study aims to understand how stem cells give rise to astrocytes in different regions of the brain during development, and whether this formative process is maintained in the adult brain when astrocytes respond to injury. We propose to further explore how specific populations of astrocytes influence normal brain function. We hypothesize that astrocyte diversity is derived through the proliferation of distinct subpopulations of stem cells during development and following injury. We will use genetic tools to trace subpopulations of astrocytes with fluorescent protein tags and map their relationships with the neural stem cells. In addition, we will use ablation and reprogramming strategies to eliminate specific subpopulations of astrocytes and assess how this impacts the normal brain function. Our research program exploring astrocyte development and function will have significant impact in the field of neurodevelopment.

人脑由两种主要细胞类型组成：神经元和神经胶质细胞。两者都来自发育过程中的神经干细胞。星形胶质细胞是大脑中含量最丰富的细胞，是胶质细胞的一种。然而，从历史上看，星形胶质细胞一直被研究得很少，因为它们被认为只是通讯神经元正常功能的支持细胞。自那以后，星形胶质细胞被证明在大脑的正常运作中发挥着重要作用。与神经元相似，它们是一个多样化的细胞群，但人们对它们如何实现这种多样性以及这种多样性与大脑功能的关系知之甚少。我们的研究旨在了解干细胞在发育过程中如何在大脑的不同区域形成星形胶质细胞，以及当星形胶质细胞对损伤做出反应时，这种形成过程是否在成年大脑中保持。我们建议进一步探索星形胶质细胞的特定群体如何影响正常的大脑功能。我们假设，星形胶质细胞的多样性是通过发育期间和损伤后不同亚群干细胞的增殖而产生的。我们将使用基因工具追踪带有荧光蛋白标签的星形胶质细胞亚群，并绘制它们与神经干细胞的关系图。此外，我们将使用消融和重新编程策略来消除特定的星形胶质细胞亚群，并评估这如何影响正常的大脑功能。我们探索星形胶质细胞发育和功能的研究计划将在神经发育领域产生重大影响。