Regulation of the ESC transcriptome by nuclear long noncoding RNAs

  1. David L. Spector1
  1. 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
  2. 2Isis Pharmaceuticals, Inc., Carlsbad, California 92010, USA
  1. Corresponding author: spector{at}cshl.edu
  • Present addresses: 3New York Genome Center, New York, NY 10013, USA; 4Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 AT, UK

Abstract

Long noncoding (lnc)RNAs have recently emerged as key regulators of gene expression. Here, we performed high-depth poly(A)+ RNA sequencing across multiple clonal populations of mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs) to comprehensively identify differentially regulated lncRNAs. We establish a biologically robust profile of lncRNA expression in these two cell types and further confirm that the majority of these lncRNAs are enriched in the nucleus. Applying weighted gene coexpression network analysis, we define a group of lncRNAs that are tightly associated with the pluripotent state of ESCs. Among these, we show that acute depletion of Platr14 using antisense oligonucleotides impacts the differentiation- and development-associated gene expression program of ESCs. Furthermore, we demonstrate that Firre, a lncRNA highly enriched in the nucleoplasm and previously reported to mediate chromosomal contacts in ESCs, controls a network of genes related to RNA processing. Together, we provide a comprehensive, up-to-date, and high resolution compilation of lncRNA expression in ESCs and NPCs and show that nuclear lncRNAs are tightly integrated into the regulation of ESC gene expression.

Footnotes

  • Received December 26, 2014.
  • Accepted June 4, 2015.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

| Table of Contents

Preprint Server