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Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis unravels new processes of adipocyte development

Nathalie Billon1*, Raivo Kolde23, Jüri Reimand2, Miguel C Monteiro1, Meelis Kull23, Hedi Peterson34, Konstantin Tretyakov2, Priit Adler4, Brigitte Wdziekonski1, Jaak Vilo23 and Christian Dani1

  • * Corresponding author: Nathalie Billon billon@unice.fr

  • † Equal contributors

Author Affiliations

1 Université de Nice Sophia-Antipolis, Institut Biologie du Développement et Cancer, CNRS UMR 6543, Faculté de Médecine Pasteur, 28 avenue de Valombrose, 06108 Nice Cedex 2, France

2 Institute of Computer Science, University of Tartu, Liivi 2, 50409, Tartu, Estonia

3 Quretec, Ülikooli 6a, 51003 Tartu, Estonia

4 Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, 51010 Tartu, Estonia

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Genome Biology 2010, 11:R80  doi:10.1186/gb-2010-11-8-r80

Published: 3 August 2010

Abstract

Background

The current epidemic of obesity has caused a surge of interest in the study of adipose tissue formation. While major progress has been made in defining the molecular networks that control adipocyte terminal differentiation, the early steps of adipocyte development and the embryonic origin of this lineage remain largely unknown.

Results

Here we performed genome-wide analysis of gene expression during adipogenesis of mouse embryonic stem cells (ESCs). We then pursued comprehensive bioinformatic analyses, including de novo functional annotation and curation of the generated data within the context of biological pathways, to uncover novel biological functions associated with the early steps of adipocyte development. By combining in-depth gene regulation studies and in silico analysis of transcription factor binding site enrichment, we also provide insights into the transcriptional networks that might govern these early steps.

Conclusions

This study supports several biological findings: firstly, adipocyte development in mouse ESCs is coupled to blood vessel morphogenesis and neural development, just as it is during mouse development. Secondly, the early steps of adipocyte formation involve major changes in signaling and transcriptional networks. A large proportion of the transcription factors that we uncovered in mouse ESCs are also expressed in the mouse embryonic mesenchyme and in adipose tissues, demonstrating the power of our approach to probe for genes associated with early developmental processes on a genome-wide scale. Finally, we reveal a plethora of novel candidate genes for adipocyte development and present a unique resource that can be further explored in functional assays.