Regulation of the ESC transcriptome by nuclear long noncoding RNAs

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...

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Bibliographic Details
Published in:Genome research 2015-09, Vol.25 (9), p.1336-1346
Main Authors: Bergmann, Jan H, Li, Jingjing, Eckersley-Maslin, Mélanie A, Rigo, Frank, Freier, Susan M, Spector, David L
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cell Nucleus
Cluster Analysis
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Gene Expression Profiling
Gene Expression Regulation
Mice
Neural Stem Cells - cytology
Neural Stem Cells - metabolism
RNA, Long Noncoding - genetics
Transcriptome
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Summary: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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.189027.114