An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex

Journal of Neuroscience - Tập 34 Số 36 - Trang 11929-11947 - 2014
Ye Zhang1, Kenian Chen2,3, Steven A. Sloan1, Mariko L. Bennett1, Anja R. Scholze1, Sean O’Keeffe4, Hemali Phatnani4, Paolo Guarnieri5,6, Christine Caneda1, Nadine Ruderisch7, Shuyun Deng2,3, Shane A. Liddelow1,8, Chaolin Zhang4,5,9, Richard Daneman7, Tom Maniatis4, Ben A. Barres1, Jia Qian Wu2,3
11Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125,
22The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, Texas 77057,
33Center for Stem Cell and Regenerative Medicine, University of Texas Brown Institute of Molecular Medicine, Houston, Texas 77057,
44Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032,
57Department of Systems Biology,
69Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032
75Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452,
86Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia 3010, and
98Center for Motor Neuron Biology and Disease, and

Tóm tắt

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 ofPKM2, 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.

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