Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene ex...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2013-01, Vol.41 (2), p.711-726
Main Authors: De Cegli, Rossella, Iacobacci, Simona, Flore, Gemma, Gambardella, Gennaro, Mao, Lei, Cutillo, Luisa, Lauria, Mario, Klose, Joachim, Illingworth, Elizabeth, Banfi, Sandro, di Bernardo, Diego
Format: Article
Language:English
Subjects:
Animals
Brain - embryology
Brain - metabolism
Cell Line
Chromosomal Proteins, Non-Histone
Computational Biology
Embryonic Stem Cells - metabolism
Gene Expression Profiling
Gene Regulatory Networks
Mice
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Neurogenesis - genetics
Protein Interaction Mapping
Systems Biology - methods
Transcriptome
Transgenes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gks1136