title: Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.
abstract: Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases.
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Dong
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Kenian
authors.initials: K
authors.lastname: Chen
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Raquel
authors.initials: R
authors.lastname: Cuevas-Diaz Duran
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Yanan
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Sloan
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Shan
authors.initials: S
authors.lastname: Zong
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston Medical School, Houston, Texas, United States of America.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas, United States of America.
authors.forename: Jia Qian
authors.initials: JQ
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000145:classification / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding