2026-08-05T15:45:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83812024-09-27T10:09:35Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19607
Repisalud
author
Scheideler, Marcel
author
Elabd, Christian
author
Zaragosi, Laure-Emmanuelle
author
Chiellini, Chiara
author
Hackl, Hubert
author
Sanchez-Cabo, Fatima
author
Yadav, Sunaina
author
Duszka, Kalina
author
Friedl, Gerald
author
Papak, Christine
author
Prokesch, Andreas
author
Windhager, Reinhard
author
Ailhaud, Gerard
author
Dani, Christian
author
Amri, Ez-Zoubir
author
Trajanoski, Zlatko
funder
French National Centre for Scientific Research (Francia)
funder
Austrian Exchange Service
funder
Fondation pour la recherche médicale (Francia)
2019-09-25T08:32:38Z
2019-09-25T08:32:38Z
2008-07
BMC Genomics. 2008; 9:340
10.1186/1471-2164-9-340
1471-2164
1471-2164
BMC genomics
18637193
http://hdl.handle.net/20.500.12105/8381
BACKGROUND: 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.
eng
Comparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesis
journal article
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