Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis unravels new processes of adipocyte development.
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.
Billon
Nathalie
N
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. billon@unice.fr
Kolde
Raivo
R
Reimand
Jüri
J
Monteiro
Miguel C
MC
Kull
Meelis
M
Peterson
Hedi
H
Tretyakov
Konstantin
K
Adler
Priit
P
Wdziekonski
Brigitte
B
Vilo
Jaak
J
Dani
Christian
C
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D016678:Genome; D051379:Mice; D014157:Transcription Factors
D014157:Transcription Factors