Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo

Abstract

SUMMARY 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.

Chromatin and RNA Maps Reveal Regulatory Long Noncoding RNAs in Mouse

“…Importantly, these lncRNAs did not contain transcripts with coding potential, as measured by the two independent methods, including conservation-independent CPAT (22) and conservation-dependent PhyloCSF (23) (see Materials and Methods). About 85% of this data set overlapped previously identified lncRNAs (17,20,(34)(35)(36)(37)(38)) (see Fig. S1 in the supplemental material), supporting the accuracy of our prediction pipeline, with a total of 34% of all known lncRNAs recovered (Fig.…”

Long Noncoding RNAs in Cardiovascular Diseases

“…Given that lncRNAs are more tissue/cell-type specifically expressed and potentially regulated than protein-coding genes, 84,85 it is assume that they should have functions during the development of an organism, including the heart. Fendrr (Fetal-lethal noncoding developmental regulatory RNA) is 1 excellent example.…”

New Lncs to mesendoderm specification

“…Currently, the best characterized lncRNAs are typically polymerase II (Pol II) transcribed, multiexonic, 5' capped, alternatively spliced and polyadenylated. LncRNAs are usually expressed at a lower level than mRNAs but importantly are characterized by a greater tissue and cell specificity (4)(5)(6)(7). Recent studies have shown that lncRNAs regulate various biological processes such as chromosome inactivation (8), imprinting (9), splicing (10) and transcriptional control (11).…”