Dataset Information

Transcriptomics profiling of human SGBS adipogenesis.

ABSTRACT: Obesity is an ever-growing epidemic where tissue homeostasis is influenced by the differentiation of adipocytes that function in lipid metabolism, endocrine and inflammatory processes. While this differentiation process has been well-characterized in mice, limited data is available from human cells. Applying microarray expression profiling in the human SGBS pre-adipocyte cell line, we identified genes with differential expression during differentiation in combination with constraint-based modeling of metabolic pathway activity. Here we describe the experimental design and quality controls in detail for the gene expression and related results published by Galhardo et al. in Nucleic Acids Research 2014 associated with the data uploaded to NCBI Gene Expression Omnibus (GSE41352).

SUBMITTER: Galhardo M

PROVIDER: S-EPMC4535456 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Transcriptomics profiling of human SGBS adipogenesis.

Galhardo Mafalda M Sinkkonen Lasse L Berninger Philipp P Lin Jake J Sauter Thomas T Heinäniemi Merja M

Genomics data 20140807

Obesity is an ever-growing epidemic where tissue homeostasis is influenced by the differentiation of adipocytes that function in lipid metabolism, endocrine and inflammatory processes. While this differentiation process has been well-characterized in mice, limited data is available from human cells. Applying microarray expression profiling in the human SGBS pre-adipocyte cell line, we identified genes with differential expression during differentiation in combination with constraint-based modeli ...[more]

PMID: 26484102

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Project description: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.

Project description:BACKGROUND: The differentiation of fibroblast-like pre-adipocytes to lipid-loaded adipocytes is regulated by a network of transcription factors, the most prominent one being the nuclear receptor peroxisome proliferator-activated receptor (PPAR) ?. However, many of the other 47 members of the nuclear receptor superfamily have an impact on adipogenesis, which in human cells has not been investigated in detail. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed by quantitative PCR all human nuclear receptors at multiple time points during differentiation of SGBS pre-adipocytes. The earliest effect was the down-regulation of the genes RARG, PPARD, REV-ERBA, REV-ERBB, VDR and GR followed by the up-regulation of PPARG, LXRA and AR. These observations are supported with data from 3T3-L1 mouse pre-adipocytes and primary human adipocytes. Investigation of the effects of the individual differentiation mix components in short-term treatments and of their omission from the full mix showed that the expression levels of the early-regulated nuclear receptor genes were most affected by the glucocorticoid receptor (GR) ligand cortisol and the phosphodiesterase inhibitor IBMX. Interestingly, the effects of both compounds converged to repress the genes PPARD, REV-ERBA, REV-ERBB, VDR and GR, whereas cortisol and IBMX showed antagonistic interaction for PPARG, LXRA and AR causing a time lag in their up-regulation. We hypothesize that the well-known auto-repression of GR fine-tunes the detected early responses. Consistently, chromatin immunoprecipitation experiments showed that GR association increased on the transcription start sites of the genes RARG, REV-ERBB, VDR and GR. CONCLUSIONS/SIGNIFICANCE: Adipocyte differentiation is a process, in which many members of the nuclear receptor superfamily change their mRNA expression. The actions of cortisol and IBMX converged to repress several nuclear receptors early in differentiation, while up-regulation of other nuclear receptor genes showed a time lag due to antagonisms of the signals. Our results place GR and its ligand cortisol as central regulatory factors controlling early regulatory events in human adipogenesis that precedes the regulation of the later events by PPARG.

Dataset Information

Transcriptomics profiling of human SGBS adipogenesis.

Publications

Transcriptomics profiling of human SGBS adipogenesis.

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