NRSF downregulation induces neuronal differentiation in mouse embryonic stem cells

Differentiation of embryonic stem (ES) cells into neurons is accompanied by global changes in transcriptional programs. One transcription factor that has been shown to be involved in neuronal differentiation is neuron restrictive silencing factor/RE1-silencing transcription factor (NRSF/REST). NRSF...

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Bibliographic Details
Published in:Differentiation (London) 2009, Vol.77 (1), p.19-28
Main Authors: Kumar Gupta, Shailesh, Gressens, Pierre, Mani, Shyamala
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Differentiation
Down-Regulation
Embryonic stem cells
Embryonic Stem Cells - metabolism
Mice
Neuroglia - metabolism
Neuron restrictive silencing factor
Neurons - cytology
Repressor Proteins - metabolism
Retinoic acid
RNA Interference
Tretinoin - metabolism
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Summary:Differentiation of embryonic stem (ES) cells into neurons is accompanied by global changes in transcriptional programs. One transcription factor that has been shown to be involved in neuronal differentiation is neuron restrictive silencing factor/RE1-silencing transcription factor (NRSF/REST). NRSF is a transcriptional repressor that silences the transcription of a large number of neuronal genes by binding to a 21-bp consensus DNA sequence, the RE1 binding site/neuron-restrictive silencer elements (RE1/NRSE), present in the regulatory regions of neuronal genes. The goal of the current study was to examine the role of NRSF during differentiation of ES cells into neurons. To do this, ShRNA construct was used to downregulate NRSF in undifferentiated ES cells. Our results show that although control ES cells required induction by retinoic acid (RA) to differentiate efficiently into neurons, downregulation of NRSF was sufficient to drive the ES cells down the neuronal lineage even in the absence of RA. This downregulation also led to increased expression of mature neuronal markers, and concomitantly decreased glial fibrillary acidic protein (GFAP) expression. The results suggest that NRSF downregulation increases the population of mature neurons at the expense of GFAP-positive cells.
ISSN:0301-4681
1432-0436
DOI:10.1016/j.diff.2008.09.001