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Genome Biology

, 11:R80

First Online: 03 August 2010Received: 04 June 2010Revised: 02 July 2010Accepted: 03 August 2010

Abstract

BackgroundThe 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.

ResultsHere 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.

ConclusionsThis 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.

AbbreviationsAFadipocyte fraction

APActivator protein

BIO2-Z,3-E-6-bromoindirubin-3-oxime

C-EBPCCAAT-enhancer-binding protein

EBembryoid body

FABP4fatty acid binding protein 4

FOXC2forkhead box C2

GOGene Ontology

GPDHglycerol-phosphate dehydrogenase

GSKglycogen synthase kinase

HIPKhomeodomain interacting protein kinase

HOXA2homeobox A2

KEGGKyoto Encyclopedia of Genes and Genomes

LPLlipoprotein lipase

MEIS1myeloid ecotropic viral integration site 1

mESCmouse embryonic stem cell

MSCmesenchymal stem cell

PAX6paired box gene 6

PBX1Pre B-cell leukemia transcription factor 1

PPARγPeroxisome proliferator-activated receptor γ

PPIprotein-protein interaction

qPCRquantitative real-time PCR

RAretinoic acid

RARretinoic acid receptor

sFRPsecreted frizzled-related protein

SVFstromal vascular fraction

TFtranscription factor

TFBStranscription factor binding site

WATwhite adipose tissue

Wntwingless-related MMTV integration site.

Electronic supplementary materialThe online version of this article doi:10.1186-gb-2010-11-8-r80 contains supplementary material, which is available to authorized users.

Raivo Kolde, Jüri Reimand, Miguel C Monteiro contributed equally to this work.

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Autor: Nathalie Billon - Raivo Kolde - Jüri Reimand - Miguel C Monteiro - Meelis Kull - Hedi Peterson - Konstantin Tretyakov - P

Fuente: https://link.springer.com/



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