title: An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.
abstract: 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.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125, zhangye@stanford.edu jiaqian.wu@uth.tmc.edu.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, Texas 77057, Center for Stem Cell and Regenerative Medicine, University of Texas Brown Institute of Molecular Medicine, Houston, Texas 77057.
authors.forename: Kenian
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Sloan
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125.
authors.forename: Mariko L
authors.initials: ML
authors.lastname: Bennett
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125.
authors.forename: Anja R
authors.initials: AR
authors.lastname: Scholze
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Keeffe
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032.
authors.forename: Hemali P
authors.initials: HP
authors.lastname: Phatnani
authors.affiliation: Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032.
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0002-6979-2638
authors.initials: P
authors.lastname: Guarnieri
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125.
authors.forename: Christine
authors.initials: C
authors.lastname: Caneda
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452.
authors.forename: Nadine
authors.initials: N
authors.lastname: Ruderisch
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, Texas 77057, Center for Stem Cell and Regenerative Medicine, University of Texas Brown Institute of Molecular Medicine, Houston, Texas 77057.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia 3010, and.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Liddelow
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032, Department of Systems Biology, Center for Motor Neuron Biology and Disease, and.
authors.forename: Chaolin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452.
authors.forename: Richard
authors.initials: R
authors.lastname: Daneman
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032.
authors.forename: Tom
authors.initials: T
authors.lastname: Maniatis
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125.
authors.forename: Ben A
authors.identifier: http://orcid.org/0000-0003-2905-4136
authors.initials: BA
authors.lastname: Barres
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, Texas 77057, Center for Stem Cell and Regenerative Medicine, University of Texas Brown Institute of Molecular Medicine, Houston, Texas 77057, zhangye@stanford.edu jiaqian.wu@uth.tmc.edu.
authors.forename: Jian Qian
authors.identifier: http://orcid.org/0000-0002-6938-6648
authors.initials: JQ
authors.lastname: Wu
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D030561:Databases, Nucleic Acid; D004730:Endothelium, Vascular / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059467:Transcriptome
keywords: alternative splicing; astrocytes; microglia; oligodendrocytes; transcriptome; vascular cells