Genetically modified IL-2 bone marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment
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PROVIDER: PRJNA977219 | ENA |
REPOSITORIES: ENA
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Project description:According to the Canadian Food Inspection Agency and Health Canada, genetically modified crops are considered safe if they are substantially equivalent to a conventional crop in regards to agronomic, physiological and compositional characteristics. A recurring issue in safety assessment of genetically modified crops is the paucity of analytical methods to detect unintended or unexpected outcomes of genetic modification. Traditional targeted compound comparative analyses are limited in scope and capacity to detect unintended changes in chemical composition. This study explored the potential of using microarray technology to assess the substantial equivalence of gene expression profiles between genetically modified and conventional soybean cultivars. Different pre processing methods were applied to the raw expression data from the arrays, and clustering methods were used to try and differentiate the genetically modified cultivars from the conventional cultivars. Results showed that more variation existed between different strains of conventional cultivars than between conventional and genetically modified cultivars. For more information, please see: Cheng, K.C., Beaulieu, J., Iquira, E., Belzile, F.J., Fortin, M.G. and Strömvik, M.V. (2008). âEffect of transgenes on global gene expression in soybean is within the natural range of variation of their conventional counterparts.â Journal of Agricultural and Food Chemistry (in press) Experiment Overall Design: Five samples (biological replicates) of total RNA from each of the five different soybean varieties were selected for hybridization to Affymetrix Soybean GeneChips, for a total of 25 chips (following total RNA integrity assessment). Spike controls B2, bio-B, bio-C, bio-D and Cre-x were added to each hybridization cocktail. Arrays were washed and stained in an Affymetrix Fluidics Station prior to scanning on the Affymetrix GeneChip Scanner 3000. Image acquisition and processing was done with the Affymetrix Microarray Analysis Suite 5.0.
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Project description:Although genetically modified glyphosate resistant soybeans with cp4-epsps gene have been widely planted all over the world, the proteomic characteristics of them are not very clear. In this study, the soybean seeds of a genetically modified (GM) soybean line H06-698 (H) with cp4-epsps gene and its non-transgenic counterpart Mengdou12 (M), which collected from different planting regions in two years, were analyzed with label-free proteomics technique.
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Project description:Myeloid-derived suppressor cells (MDSCs), which accumulate in tumor bearers, are known to suppress anti-tumor immunity and thus promote tumor progression. MDSCs are considered a major cause of resistance against immune checkpoint inhibitors in patients with cancer. Therefore, MDSCs are potential targets in cancer immunotherapy. In this study, we modified an in vitro method of MDSC differentiation. Upon stimulating bone marrow (BM) cells with granulocyte-macrophage colony-stimulating factor in vitro, we obtained both lymphocyte antigen 6G positive (Ly-6G+) and negative (Ly-6G−) MDSCs (collectively, hereafter referred to as conventional MDSCs), which were non-immunosuppressive and immunosuppressive, respectively. We then found that MDSCs differentiated from Ly-6G− BM (hereafter called 6G− BM-MDSC) suppressed T-cell proliferation more strongly than conventional MDSCs, whereas the cells differentiated from Ly-6G+ BM (hereafter called 6G+ BM-MDSC) were non-immunosuppressive. In line with this, conventional MDSCs or 6G− BM-MDSC, but not 6G+ BM-MDSC, promoted tumor progression in tumor-bearing mice. Moreover, we identified that activated glutathione metabolism was responsible for the enhanced immunosuppressive ability of 6G− BM-MDSC. Finally, we showed that Ly-6G+ cells in 6G− BM-MDSC, which exhibited weak immunosuppression, expressed higher levels of Cybb mRNA, an immunosuppressive gene of MDSCs, than 6G+ BM-MDSC. Together, these data suggest that the depletion of Ly-6G+ cells from the BM cells leads to differentiation of immunosuppressive Ly-6G+ MDSCs. In summary, we propose a better method for MDSC differentiation in vitro. Moreover, our findings contribute to the understanding of MDSC subpopulations and provide a basis for further research on MDSCs.
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