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dc.contributor.authorScheideler, Marcel
dc.contributor.authorElabd, Christian
dc.contributor.authorZaragosi, Laure-Emmanuelle
dc.contributor.authorChiellini, Chiara
dc.contributor.authorHackl, Hubert
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorYadav, Sunaina
dc.contributor.authorDuszka, Kalina
dc.contributor.authorFriedl, Gerald
dc.contributor.authorPapak, Christine
dc.contributor.authorProkesch, Andreas
dc.contributor.authorWindhager, Reinhard
dc.contributor.authorAilhaud, Gerard
dc.contributor.authorDani, Christian
dc.contributor.authorAmri, Ez-Zoubir
dc.contributor.authorTrajanoski, Zlatko
dc.identifier.citationBMC Genomics. 2008; 9:340es_ES
dc.description.abstractBACKGROUND: A reciprocal relationship between bone and fat development in osteoporosis is clinically well established. Some of the key molecular regulators involved in this tissue replacement process have been identified. The detailed mechanisms governing the differentiation of mesenchymal stem cells (MSC) - the key cells involved - are however only now beginning to emerge. In an attempt to address the regulation of the adipocyte/osteoblast balance at the level of gene transcription in a comprehensive and unbiased manner, we performed a large-scale gene expression profiling study using a unique cellular model, human multipotent adipose tissue-derived stem cells (hMADS). RESULTS: The analysis of 1606 genes that were found to be differentially expressed between adipogenesis and osteoblastogenesis revealed gene repression to be most prevalent prior to commitment in both lineages. Computational analyses suggested that this gene repression is mediated by miRNAs. The transcriptional activation of lineage-specific molecular processes in both cases occurred predominantly after commitment. Analyses of the gene expression data and promoter sequences produced a set of 65 genes that are candidates for genes involved in the process of adipocyte/osteoblast commitment. Four of these genes were studied in more detail: LXRalpha and phospholipid transfer protein (PLTP) for adipogenesis, the nuclear receptor COUP-TF1 and one uncharacterized gene, TMEM135 for osteoblastogenesis. PLTP was secreted during both early and late time points of hMADS adipocyte differentiation. LXRalpha, COUP-TF1, and the transmembrane protein TMEM135 were studied in primary cultures of differentiating bone marrow stromal cells from healthy donors and were found to be transcriptionally activated in the corresponding lineages. CONCLUSION: Our results reveal gene repression as a predominant early mechanism before final cell commitment. We were moreover able to identify 65 genes as candidates for genes controlling the adipocyte/osteoblast balance and to further evaluate four of these. Additional studies will explore the precise role of these candidate genes in regulating the adipogenesis/osteoblastogenesis switch.es_ES
dc.description.sponsorshipThis work was supported by the GEN-AU projects BIN, GOLD, and Identification of MiRNAs Targeting Early Human Adipogenesis, by the FWF SFB project Lipotoxicity, by the Centre Nationale de la Recherche Scientifique, by a grant from 'Equipe FRM, soutenue par la Fondation pour la Recherche Medicale', by INCa (grant PL 079), and by the Amadée programme of the Austrian Exchange Service (OEAD). CC is a recipient of a fellowship from Fondation pour la Recherche Médicale.es_ES
dc.publisherBiomed Centrales_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.mesh3' Untranslated Regions es_ES
dc.subject.meshAdipogenesis es_ES
dc.subject.meshCell Line es_ES
dc.subject.meshCell Lineage es_ES
dc.subject.meshComputational Biology es_ES
dc.subject.meshDown-Regulation es_ES
dc.subject.meshGene Expression Regulation, Developmental es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMicroRNAs es_ES
dc.subject.meshModels, Genetices_ES
dc.subject.meshMultipotent Stem Cells es_ES
dc.subject.meshOligonucleotide Array Sequence Analysis es_ES
dc.subject.meshOsteoblasts es_ES
dc.subject.meshPromoter Regions, Genetices_ES
dc.subject.meshRNA es_ES
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction es_ES
dc.subject.meshTime Factors es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.titleComparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesises_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderCentre Nationale de la Recherche Scientifique (France)es_ES
dc.contributor.funderAustrian Exchange Servicees_ES
dc.contributor.funderFoundation pour la Recherche Medicalees_ES
dc.identifier.journalBMC genomicses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionaleses_ES

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Atribución 4.0 Internacional
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