Understanding astrocyte heterogeneity

大脑由两种主要细胞类型组成，神经元和神经胶质细胞，这两种细胞是在发育过程中由干细胞产生的。星形胶质细胞是胶质细胞的一种，历史上一直没有得到充分的研究，因为它们被认为是简单的支持细胞，只存在于帮助神经元功能。虽然现在人们已经接受星形胶质细胞是一个多样化的细胞群体，但他们的多样性是如何建立起来的还不是很清楚。我们的长期目标是确定不同的星形胶质细胞在大脑中是如何产生的。我们将通过基因出生测定和谱系追踪的方法，研究星形胶质细胞的多样性是否编码在干细胞中，在发育过程中星形胶质细胞来自干细胞。此外，我们还将描述我们最近在成人体内发现的一组星形胶质细胞的多样性，这些星形胶质细胞是由干细胞在损伤后重新产生的。我们将使用无偏见的测序方法来确定单个成人干细胞来源的星形胶质细胞的分子图谱，从而确定该群体中的异质性。总之，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脑发育的基本理解。这些研究还将为未来的研究提供基础，这些研究将探讨指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。这项研究计划将吸引高素质的人才。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，并为学员提供具有竞争力的技能，从而提高他们的就业能力，从而使加拿大的学术界和工业界都受益。

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.