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Transcription Adaptation during In Vitro Adipogenesis and Osteogenesis of Porcine Mesenchymal Stem Cells: Dynamics of Pathways, Biological Processes, Up-Stream Regulators, and Gene Networks.

Bionaz M, Monaco E, Wheeler MB - PLoS ONE (2015)

Bottom Line: Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis.Between MSCs the data indicated an 'adipocyte memory' in ASC with also an apparent lower immunogenicity compared to BMSC during differentiations.Overall the analysis allowed proposing a dynamic model for the adipogenic and osteogenic differentiation in porcine ASC and BMSC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell Biology and Engineering in the Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
The importance of mesenchymal stem cells (MSC) for bone regeneration is growing. Among MSC the bone marrow-derived stem cells (BMSC) are considered the gold standard in tissue engineering and regenerative medicine; however, the adipose-derived stem cells (ASC) have very similar properties and some advantages to be considered a good alternative to BMSC. The molecular mechanisms driving adipogenesis are relatively well-known but mechanisms driving osteogenesis are poorly known, particularly in pig. In the present study we have used transcriptome analysis to unravel pathways and biological functions driving in vitro adipogenesis and osteogenesis in BMSC and ASC. The analysis was performed using the novel Dynamic Impact Approach and functional enrichment analysis. In addition, a k-mean cluster analysis in association with enrichment analysis, networks reconstruction, and transcription factors overlapping analysis were performed in order to uncover the coordination of biological functions underlining differentiations. Analysis indicated a larger and more coordinated transcriptomic adaptation during adipogenesis compared to osteogenesis, with a larger induction of metabolism, particularly lipid synthesis (mostly triglycerides), and a larger use of amino acids for synthesis of feed-forward adipogenic compounds, larger cell signaling, lower cell-to-cell interactions, particularly for the cytoskeleton organization and cell junctions, and lower cell proliferation. The coordination of adipogenesis was mostly driven by Peroxisome Proliferator-activated Receptors together with other known adipogenic transcription factors. Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis. Up-stream transcription factor analysis indicated activation of several lipid-related transcription regulators (e.g., PPARs and CEBPα) during adipogenesis but osteogenesis was driven by inhibition of several up-stream regulators, such as MYC. Between MSCs the data indicated an 'adipocyte memory' in ASC with also an apparent lower immunogenicity compared to BMSC during differentiations. Overall the analysis allowed proposing a dynamic model for the adipogenic and osteogenic differentiation in porcine ASC and BMSC.

No MeSH data available.


Gene ontology biological process terms.Direction of the impact of GO Biological process terms with the largest difference in the overall direction of the impact in adipogenesis compared to osteogenesis as calculated by the Dynamic Impact Approach. The two upper rows of figures report the terms with the largest overall direction of the impact in adipogenesis compared to osteogenesis. The last two rows of figures report the terms with the largest overall direction of the impact in osteogenesis compared to adipogenesis. The full results are available in S3 File.
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pone.0137644.g005: Gene ontology biological process terms.Direction of the impact of GO Biological process terms with the largest difference in the overall direction of the impact in adipogenesis compared to osteogenesis as calculated by the Dynamic Impact Approach. The two upper rows of figures report the terms with the largest overall direction of the impact in adipogenesis compared to osteogenesis. The last two rows of figures report the terms with the largest overall direction of the impact in osteogenesis compared to adipogenesis. The full results are available in S3 File.

Mentions: In Fig 5 is reported the direction of the impact of the GO Biological processes (calculated by DIA) with the largest difference in the direction of the impact between adipogenesis and osteogenesis. The adipogenic differentiation, contrary to the osteogenic one, was featured by an overall very high impact of GO terms related to triglycerides synthesis with an evident large importance of glycerol transport and metabolism of fatty acids. The increase in glycerol transport, together with a lack of increase in utilization of glucose (as indicated by the KEGG pathway analysis, see Fig 3, and S2 File, sheet ‘KEGG pathway’), indicates a strong dependence of the differentiating MSC from the extracellular provision of glycerol for triglycerides synthesis. The adipogenesis was induced by addition of 1 μM of dexamethasone [17]. This compound is known in adipocytes to bind the glucocorticoid receptor and decrease expression of phosphoenolpyruvate carboxykinase (PCK1) by reducing the binding of several other factors (including CEBPs) to the promoter region of the PCK1 [61] inhibiting the glyceroneogenesis [62]. The latter appears to have a crucial role in triacylglycerol formation in mature adipocytes, particularly when there is an active lipolysis in adipocytes [62]. The suggested increase in glycerol transport and the latter observations suggest a minor role of glyceroneogenesis during adipogenic differentiation in our experimental conditions.


Transcription Adaptation during In Vitro Adipogenesis and Osteogenesis of Porcine Mesenchymal Stem Cells: Dynamics of Pathways, Biological Processes, Up-Stream Regulators, and Gene Networks.

Bionaz M, Monaco E, Wheeler MB - PLoS ONE (2015)

Gene ontology biological process terms.Direction of the impact of GO Biological process terms with the largest difference in the overall direction of the impact in adipogenesis compared to osteogenesis as calculated by the Dynamic Impact Approach. The two upper rows of figures report the terms with the largest overall direction of the impact in adipogenesis compared to osteogenesis. The last two rows of figures report the terms with the largest overall direction of the impact in osteogenesis compared to adipogenesis. The full results are available in S3 File.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580618&req=5

pone.0137644.g005: Gene ontology biological process terms.Direction of the impact of GO Biological process terms with the largest difference in the overall direction of the impact in adipogenesis compared to osteogenesis as calculated by the Dynamic Impact Approach. The two upper rows of figures report the terms with the largest overall direction of the impact in adipogenesis compared to osteogenesis. The last two rows of figures report the terms with the largest overall direction of the impact in osteogenesis compared to adipogenesis. The full results are available in S3 File.
Mentions: In Fig 5 is reported the direction of the impact of the GO Biological processes (calculated by DIA) with the largest difference in the direction of the impact between adipogenesis and osteogenesis. The adipogenic differentiation, contrary to the osteogenic one, was featured by an overall very high impact of GO terms related to triglycerides synthesis with an evident large importance of glycerol transport and metabolism of fatty acids. The increase in glycerol transport, together with a lack of increase in utilization of glucose (as indicated by the KEGG pathway analysis, see Fig 3, and S2 File, sheet ‘KEGG pathway’), indicates a strong dependence of the differentiating MSC from the extracellular provision of glycerol for triglycerides synthesis. The adipogenesis was induced by addition of 1 μM of dexamethasone [17]. This compound is known in adipocytes to bind the glucocorticoid receptor and decrease expression of phosphoenolpyruvate carboxykinase (PCK1) by reducing the binding of several other factors (including CEBPs) to the promoter region of the PCK1 [61] inhibiting the glyceroneogenesis [62]. The latter appears to have a crucial role in triacylglycerol formation in mature adipocytes, particularly when there is an active lipolysis in adipocytes [62]. The suggested increase in glycerol transport and the latter observations suggest a minor role of glyceroneogenesis during adipogenic differentiation in our experimental conditions.

Bottom Line: Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis.Between MSCs the data indicated an 'adipocyte memory' in ASC with also an apparent lower immunogenicity compared to BMSC during differentiations.Overall the analysis allowed proposing a dynamic model for the adipogenic and osteogenic differentiation in porcine ASC and BMSC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell Biology and Engineering in the Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
The importance of mesenchymal stem cells (MSC) for bone regeneration is growing. Among MSC the bone marrow-derived stem cells (BMSC) are considered the gold standard in tissue engineering and regenerative medicine; however, the adipose-derived stem cells (ASC) have very similar properties and some advantages to be considered a good alternative to BMSC. The molecular mechanisms driving adipogenesis are relatively well-known but mechanisms driving osteogenesis are poorly known, particularly in pig. In the present study we have used transcriptome analysis to unravel pathways and biological functions driving in vitro adipogenesis and osteogenesis in BMSC and ASC. The analysis was performed using the novel Dynamic Impact Approach and functional enrichment analysis. In addition, a k-mean cluster analysis in association with enrichment analysis, networks reconstruction, and transcription factors overlapping analysis were performed in order to uncover the coordination of biological functions underlining differentiations. Analysis indicated a larger and more coordinated transcriptomic adaptation during adipogenesis compared to osteogenesis, with a larger induction of metabolism, particularly lipid synthesis (mostly triglycerides), and a larger use of amino acids for synthesis of feed-forward adipogenic compounds, larger cell signaling, lower cell-to-cell interactions, particularly for the cytoskeleton organization and cell junctions, and lower cell proliferation. The coordination of adipogenesis was mostly driven by Peroxisome Proliferator-activated Receptors together with other known adipogenic transcription factors. Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis. Up-stream transcription factor analysis indicated activation of several lipid-related transcription regulators (e.g., PPARs and CEBPα) during adipogenesis but osteogenesis was driven by inhibition of several up-stream regulators, such as MYC. Between MSCs the data indicated an 'adipocyte memory' in ASC with also an apparent lower immunogenicity compared to BMSC during differentiations. Overall the analysis allowed proposing a dynamic model for the adipogenic and osteogenic differentiation in porcine ASC and BMSC.

No MeSH data available.