title: Regulation of the ESC transcriptome by nuclear long noncoding RNAs.
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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Jan H
authors.initials: JH
authors.lastname: Bergmann
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Mélanie A
authors.initials: MA
authors.lastname: Eckersley-Maslin
authors.affiliation: Isis Pharmaceuticals, Inc., Carlsbad, California 92010, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Rigo
authors.affiliation: Isis Pharmaceuticals, Inc., Carlsbad, California 92010, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Freier
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: David L
authors.initials: DL
authors.lastname: Spector
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding