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Next Generation Sequencing Facilitates Quantitative Analysis of human multiple myeloma derived CD84 activated M-MDSCs or IgG (control) treated M-MDSCs

ABSTRACT: Next Generation Sequencing Facilitates Quantitative Analysis of human multiple myeloma derived CD84 activated M-MDSCs or IgG (control) treated M-MDSCs

PROVIDER: PRJNA691507 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13416100_1.fastq.gz	Fastqsanger.gz
	SRR13416100_2.fastq.gz	Fastqsanger.gz
	SRR13416101_1.fastq.gz	Fastqsanger.gz
	SRR13416101_2.fastq.gz	Fastqsanger.gz
	SRR13416102_1.fastq.gz	Fastqsanger.gz

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Next Generation Sequencing Facilitates Quantitative Analysis of human multiple myeloma derived CD84 activated M-MDSCs or IgG (control) treated M-MDSCs

Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare CD84 activated to control treated primary human M-MDSCs from multiple myeloma patients transcriptome profiling (RNA-seq) to understand the role of CD84 on these cells Methods: mRNA profiles from sorted M-MDSCs from patient bone marrow samples were generated by deep sequencing, in triplicate, using a bulk adaptation of the MARS-Seq protocol.

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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare CD84 activated to control treated primary human G-MDSCs from multiple myeloma patients transcriptome profiling (RNA-seq) to understand the role of CD84 on these cells Methods: mRNA profiles from sorted G-MDSCs from patient bone marrow samples were generated by deep sequencing, in triplicate, using a bulk adaptation of the MARS-Seq protocol.

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Next Generation Sequencing Facilitates Quantitative Analysis of human multiple myeloma derived CD84 activated G-MDSCs or IgG (control) treated G-MDSCs

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Project description:Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were down-regulated, but pro-tumor function-related genes were up-regulated in both Mo-MDSCs and PMN-MDSCs at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo- and PMN-MDSCs isolated from the late time points. Experiments using siRNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing iNOS, ARG1, and ROS levels and enhancing NF-kappaB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs. To identify the factors that licensed MDSCs to be more suppressive as tumors grow, we analyzed gene expression profiles in the two subsets of MDSCs at different time points (3wks, 6wks) during tumor progression. CD11b+Ly-6C(high)Ly-6G(low) Mo-MDSCs and CD11b+Ly-6C(low)Ly-6G(high) PMN-MDSCs were sorted from pooled spleens of naÃ¯ve mice and Her-2/CT26 tumor-bearing mice. Total RNA was purified and gene expression was analyzed by the Affymetrix GeneChipÂ® Mouse Gene 1.0 ST Array.

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