Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo.

Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo.
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DOI:
10.1016/j.stem.2013.03.003
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发表时间:
2013-05-02
期刊:
影响因子:
23.9
通讯作者:
Lim, Daniel A.
Lim, Daniel A.
中科院分区:
医学1区
文献类型:
--
作者:
Ramos, Alexander D.;Diaz, Aaron;Nellore, Abhinav;Delgado, Ryan N.;Park, Ki-Youb;Gonzales-Roybal, Gabriel;Oldham, Michael C.;Song, Jun S.;Lim, Daniel A.

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长链非编码RNA(lncRNA)已在细胞系和各种完整组织中被描述,但lncRNA在体内发育的分析是有限的。在这里,我们全面分析lncRNA表达的成年小鼠脑室下区神经干细胞系。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。通过整合来自染色质状态图、定制微阵列和室管膜下区谱系的FACS纯化的数据,我们严格鉴定了在成人神经发生中具有潜在作用的lncRNA。shRNA介导的两种此类lncRNA Six 3 os和Dlx 1as的敲低表明lncRNA在多能成体干细胞的神经胶质-神经元谱系特化中的作用。因此,我们的数据和工作流程提供了一个独特的连贯的体内lncRNA分析,并形成了一个用户友好的在线资源的基础,用于研究lncRNA在发展和疾病。
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.
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