Transcriptomic profiling and integrated bioinformatic analyses of glial cell types of the brain

越来越多的证据表明，胶质细胞类型的异质性有助于更高层次的脑功能。例如，星形胶质细胞在发育过程中调节突触发生和维持成熟大脑中神经元的代谢完整性方面至关重要。在拟议的项目中，我们与几个合作伙伴一起，旨在对来自不同大脑区域和发育阶段的MACS，FACS和RiboTag纯化的胶质细胞群进行深度测序，以生成全面的胶质细胞分子目录。深入的生物信息学分析和可视化将用于建立一个数据库，以供后续查询和公众访问。通过分析在出生后早期发育阶段收获的皮质星形胶质细胞的转录组，我们确定了几个星形胶质细胞表达的基因，这些基因与突触发生和代谢支持有关。然而，对于大多数这些发育调控基因，其功能尚不清楚。我们将应用生物信息学指导的选择和实验验证筛选相结合的方法来鉴定新型星形胶质细胞表达的基因和机制，这些基因和机制在发育过程中和成年大脑中调节神经元活动。

Increasing evidence suggest that glial cell type heterogeneity contributes to higher order brain functions. Astroglial cells, for example, are essential in modulate in synaptogenesis during development and maintaining the metabolic integrity of neurons in the mature brain. In the proposed project and with several partners, we aim at applying deep sequencing of MACS, FACS and RiboTag purified glial cell populations from different brain regions and developmental stages to generate a comprehensive molecular catalogue of glia. In depth bioinformatic analyses and visualizations will be used to setup a database for follow up queries and public accessibility. By analyzing the transcriptomes of cortical astrocytes harvested at early postnatal developmental stages, we identified several astrocyte expressed genes which have been implicated in synaptogenesis and metabolic support. For most of these developmentally regulated genes, however, the function is not known. We will apply a combined biofinformatic guided selection and experimental validation screen to identify novel astrocyte expressed genes and mechanisms which modulate neuronal activity during development and in the adult brain.