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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from THP-1 cells and THP-1 cells stimulated with PMA

ABSTRACT: Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation. THP-1s were differentiated into macrophage like cells by PMA stimulation.

ORGANISM(S): Homo sapiens

SUBMITTER: Jessica Winkler

PROVIDER: E-GEOD-53691 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Inhibition of EZH2 in THP-1 cells

Project description:Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation. THP-1s were treated with the EZH2 inhibitor GSK126 for phenotypic and genotypic analysis.

2015-08-04 | E-GEOD-71671 | biostudies-arrayexpress

Expression data from THP-1 cells and THP-1 cells stimulated with PMA

2013-12-28 | GSE53691 | GEO

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2015-08-04 | GSE71671 | GEO

Expression data from monocytes and monocyte derived macrophages

Project description:Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation. Monocytes isolated from human peripherial mononuclear cells were differentiated in monocyte derived macrophages by M-CSF stimulation

2013-11-22 | E-GEOD-52647 | biostudies-arrayexpress

Expression data from monocytes and monocyte derived macrophages

2013-11-22 | GSE52647 | GEO

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Analysis of mixed-oxysterol treatment on the THP-1 macrophage

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2017-03-15 | PXD004304 | Pride

miRNA profile of THP-1 macrophage infected with different MTB strains

Project description:We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of (1) Beijing/W and non-Beijing/W clinical strains, and (2) susceptible and multidrug-resistant (MDR-) MTB strains. THP-1 cells were induced differentiation into a macrophage phenotype. Then cells were infected with three MDR (INHR, RIFR) Beijing/W, three sensitive (INHS, RIFS) Beijing/W, three MDR(INHR, RIFR) non-Beijing/W, and three sensitive (INHS, RIFS) non-Beijing/W strains. Total RNA were extracted and transfered into cDNA for miRNA profile analysis. Non-infected cells were used as control.

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