EXPERIMENT_TITLE: GSM6234166: p1_G; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: NK cells were separated from NG-BM and G-BM using FACS 2 million cells per sample were fixed with 1% formaldehyde and suspended in Hi-C lysis buffer, then 100U MobI restriction enzyme (NEB, R0147) was added. After overnight chromatin digestion, biotin was used to fill ends before DNA proximity ligation and crosslink. Then DNA was sheared to 300-500 bp using sonicator. Finally, biotin-labeled DNA was pulled down and libraries were prepared using the NEBNext primer set and sequenced on Illumina HiSeq X Ten.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-?). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-? secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identified a pathway that was activated in response to G-CSF treatment, which suppressed IFN-? secretion in NK cells. Specifically, our integrative genomic strategy revealed glucocorticoid receptor (GR) activation in NK cells that mediated the genomic response to G-CSF treatment. Activated GRs can inhibit secretion of IFN-? by promoting interactions between suppressor of cytokine signaling 1 (SOCS1) promoter and enhancer, as well as increase the expression of SOCS1. Experiments in mice confirmed that G-CSF in vivo treatment significantly down-regulated IFN-? secretion and up-regulated GR and SOCS1 expression in NK cells. In addition, GR blockade (RU486) significantly reversed the effects of G-CSF, demonstrating that GR up-regulates SOCS1 and inhibits the production of IFN-? by NK cells. Overall design: This study was designed to explore the mechanism of the suppression effect  of G-CSF on IFN-? production. To this end, we generated multi-omics profile of HSC donor derived bone marrow NK cells before and after G-CSF treatment and further validated our findings in mice.
SAMPLE_TITLE: p1_G
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "bone marrow"}, {"TAG": "tissue", "VALUE": "bone marrow"}, {"TAG": "cell line", "VALUE": "primary cells"}, {"TAG": "cell type", "VALUE": "NK cells"}, {"TAG": "genotype", "VALUE": "WT"}, {"TAG": "treatment", "VALUE": "after G-CSF treatment"}]
Pool_Member_@attributes_sample_title: p1_G
RUN_SET_RUN_Pool_Member_@attributes_sample_title: p1_G
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