Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation

Tim R. Mercer, Irfan A. Qureshi, Solen Gokhan, Marcel E. Dinger, Guangyu Li, John S. Mattick, Mark F. Mehler

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

Background: Long non-protein-coding RNAs (ncRNAs) are emerging as important regulators of cellular differentiation and are widely expressed in the brain.Results: Here we show that many long ncRNAs exhibit dynamic expression patterns during neuronal and oligodendrocyte (OL) lineage specification, neuronal-glial fate transitions, and progressive stages of OL lineage elaboration including myelination. Consideration of the genomic context of these dynamically regulated ncRNAs showed they were part of complex transcriptional loci that encompass key neural developmental protein-coding genes, with which they exhibit concordant expression profiles as indicated by both microarray and in situ hybridization analyses. These included ncRNAs associated with differentiation-specific nuclear subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental enhancers and genes encoding important transcription factors and homeotic proteins. We also observed changes in ncRNA expression profiles in response to treatment with trichostatin A, a histone deacetylase inhibitor that prevents the progression of OL progenitors into post-mitotic OLs by altering lineage-specific gene expression programs.Conclusion: This is the first report of long ncRNA expression in neuronal and glial cell differentiation and of the modulation of ncRNA expression by modification of chromatin architecture. These observations explicitly link ncRNA dynamics to neural stem cell fate decisions, specification and epigenetic reprogramming and may have important implications for understanding and treating neuropsychiatric diseases.

Original languageEnglish (US)
Article number14
JournalBMC Neuroscience
Volume11
DOIs
StatePublished - Feb 5 2010

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Long Noncoding RNA
Untranslated RNA
Oligodendroglia
Neuroglia
trichostatin A
Developmental Genes
Homeodomain Proteins
Histone Deacetylase Inhibitors
Neural Stem Cells
Epigenomics
Chromatin
In Situ Hybridization
Cell Differentiation
Transcription Factors
Gene Expression
Brain
Proteins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

Cite this

Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. / Mercer, Tim R.; Qureshi, Irfan A.; Gokhan, Solen; Dinger, Marcel E.; Li, Guangyu; Mattick, John S.; Mehler, Mark F.

In: BMC Neuroscience, Vol. 11, 14, 05.02.2010.

Research output: Contribution to journalArticle

Mercer, Tim R. ; Qureshi, Irfan A. ; Gokhan, Solen ; Dinger, Marcel E. ; Li, Guangyu ; Mattick, John S. ; Mehler, Mark F. / Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. In: BMC Neuroscience. 2010 ; Vol. 11.
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