An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
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DOI：
10.11772/j.issn.1001-9081.2014.07.1929
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发表时间：
2014-09-03
影响因子：
5.3
通讯作者：
Wu, Jia Qian
中科院分区：
文献类型：
--
作者：
Zhang, Ye;Chen, Kenian;Wu, Jia Qian
大脑的主要细胞类别在发育过程、新陈代谢、信号传导和功能方面有所不同。为了更好地了解组成这些类别的细胞类型的功能和相互作用，我们从小鼠大脑皮层中急性纯化了神经元、星形胶质细胞、少突胶质细胞前体细胞、新形成的少突胶质细胞、髓鞘化少突胶质细胞、小胶质细胞、内皮细胞和周细胞的代表性群体。我们通过 RNA 测序生成了这八种细胞类型的转录组数据库，并使用灵敏的算法来检测每种细胞类型中的选择性剪接事件。生物信息学分析发现了数千个新的细胞类型丰富的基因和剪接亚型，这将为细胞识别提供新的标记、基因操作的工具以及对大脑生物学的深入了解。例如，我们的数据提供了关于神经元和星形胶质细胞在动态调节糖酵解通量和乳酸生成的能力方面有何不同的线索，这归因于PKM2（编码糖酵解酶丙酮酸激酶的基因）的独特剪接。该数据集将为理解大脑的发育和功能提供强大的新资源。为了确保这些数据集的广泛分发，我们创建了一个用户友好的网站（http://web.stanford.edu/group/barres_lab/brain_rnaseq.html），该网站提供了一个用于分析和比较大脑中各种细胞类别的转录和选择性剪接概况的平台。
The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain.