Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Stem Cell. 2013 May 2;12(5):616-28. doi: 10.1016/j.stem.2013.03.003. Epub 2013 Apr 11.
Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease.
长链非编码 RNA（lncRNA）已在细胞系和各种组织中进行了描述，但体内发育的 lncRNA 分析受到限制。在这里，我们全面分析了成年小鼠侧脑室下区神经干细胞谱系的 lncRNA 表达。我们利用互补的全基因组技术，包括 RNA-seq、RNA CaptureSeq 和 ChIP-seq，将特定的 lncRNA 与神经细胞类型、发育过程和人类疾病状态相关联。通过整合染色质状态图谱、定制微阵列和侧脑室下区谱系的 FACS 纯化的数据，我们严格地鉴定了在成人神经发生中具有潜在作用的 lncRNA。通过 shRNA 介导的两种此类 lncRNA（Six3os 和 Dlx1as）的敲低，表明 lncRNA 在多能成体干细胞的胶质-神经元谱系特化中发挥作用。我们的数据和工作流程因此提供了独特的、一致的体内 lncRNA 分析，并为发育和疾病中 lncRNA 研究的用户友好型在线资源奠定了基础。
