Understanding astrocyte heterogeneity

了解星形胶质细胞异质性

• 批准号: RGPIN-2020-06512
• 负责人: Faiz, Maryam
• 金额: $ 2.19万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740761
• 关键词: Understanding; astrocyte; heterogeneity

The brain is composed of two main cell types, neurons and glia, which are produced from stem cells during development. Astrocytes, one type of glial cell, have historically been understudied because they were thought to be simple support cells present only to aid neuronal function. While it is now accepted that astrocytes are a diverse population of cells, how their diversity is established is not well understood. Our long-term goal is to determine how different astrocyte identities are created in the brain. We will investigate whether astrocyte diversity is coded in the stem cells from which they originate during development by using genetic birthdating and lineage tracing approaches. In addition, we will characterize the diversity of a subset of astrocytes we recently discovered in the adult that are produced de novo from stem cells in response to injury. We will use unbiased sequencing methods to determine the molecular profile of individual adult stem cell-derived astrocytes cells and thus, the heterogeneity within this population. Altogether, the study of astrocyte diversity will improve our fundamental understanding of astrocyte biology and brain development. These studies will also provide a foundation for future research that will investigate the mechanisms that specify different astrocyte subsets and if/how different astrocyte subpopulations contribute to neurodevelopmental and neurodegenerative diseases. This research program will attract highly qualified personnel. The training they receive in my laboratory will include state of the art methods and equipment and give trainees a competitive skill set that will increase their employability, thus benefitting both academia and industry in Canada.

大脑由两种主要细胞类型组成：神经元和神经胶质细胞，它们是在发育过程中由干细胞产生的。星形胶质细胞是神经胶质细胞的一种，历史上一直没有得到充分研究，因为它们被认为是仅帮助神经元功能的简单支持细胞。虽然现在人们普遍认为星形胶质细胞是一个多样化的细胞群，但它们的多样性是如何建立的尚不清楚。 我们的长期目标是确定大脑中如何产生不同的星形胶质细胞特性。我们将通过使用遗传出生日期和谱系追踪方法来研究星形胶质细胞多样性是否在发育过程中起源的干细胞中编码。此外，我们将描述我们最近在成人中发现的星形胶质细胞亚群的多样性，这些星形胶质细胞是由干细胞响应损伤而从头产生的。我们将使用无偏测序方法来确定单个成体干细胞衍生的星形胶质细胞的分子特征，从而确定该群体内的异质性。总而言之，星形胶质细胞多样性的研究将提高我们对星形胶质细胞生物学和大脑发育的基本理解。这些研究还将为未来的研究奠定基础，这些研究将调查特定不同星形胶质细胞亚群的机制以及不同星形胶质细胞亚群是否/如何导致神经发育和神经退行性疾病。 该研究计划将吸引高素质人才。他们在我的实验室接受的培训将包括最先进的方法和设备，并为学员提供有竞争力的技能，这将提高他们的就业能力，从而使加拿大的学术界和工业界受益。