Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12274319_1.fastq.gz | Fastqsanger.gz | |||
| SRR12274319_2.fastq.gz | Fastqsanger.gz | |||
| SRR12274320_1.fastq.gz | Fastqsanger.gz | |||
| SRR12274320_2.fastq.gz | Fastqsanger.gz | |||
| SRR12274321_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:SOCS1 is a tumor suppressor in hepatocellular carcinoma. Recently we showed that loss of SOCS1 in hepatocytes promotes NRF2 activation. Here we investigated how SOCS1 expression affected oxidative stress response in HCC cells. Murine Hepa1-6 cells expressing SOCS1 (Hepa-SOCS1) or control vector (Hepa-Vector) were treated with cisplatin or tert-butyl hydroperoxide (t-BHP). Induction of NRF2 and its target genes, oxidative stress, lipid peroxidation, cell survival and cellular proteome profiles were evaluated. NRF2 induction was significantly reduced in Hepa-SOCS1 cells. The gene and protein expression of NRF2 targets were differentially induced in Hepa-Vector cells but markedly suppressed in Hepa-SOCS1 cells. Hepa-SOCS1 cells displayed increased induction of reactive oxygen species (ROS) but reduced lipid peroxidation. Nonetheless, Hepa-SOCS1 cells treated with cisplatin or t-BHP showed reduced survival. GCLC, poorly induced in Hepa-SOCS1 cells, showed a strong positive correlation with NFE2L2 and an inverse correlation with SOCS1 in the TCGA-LIHC transcriptomic data. Proteomic analysis of Hepa-Vector and Hepa-SOCS1 cells revealed that SOCS1 differentially modulated many proteins involved in diverse molecular pathways including those implicated in mitochondrial ROS generation and detoxification by peroxiredoxin and thioredoxin systems. Our findings indicate that maintaining sensitivity to oxidative stress is an important tumor suppression mechanism of SOCS1 in HCC.
2024-05-22 | PXD047908 | Pride
Project description:Suppressor of Cytokine Signaling 1 (SOCS1) functions as a tumor suppressor in hepatocellular carcinoma by regulating cytokine, growth factor and other signaling pathways. The tumor suppressor functions of SOCS1 are mediated partly via promoting ubiquitination and proteasomal degradation of several signaling proteins. In this study, we used an unbiased approach to characterize SOCS1-mediated changes in the protein profile of hepatocytes. The murine HCC cell line Hepa1-6 transduced with wildtype SOCS1, an SH2 domain mutant or the empty lentiviral vector were grown in Stable Isotopic Labelling of Amino acids in Cell culture (SILAC) media. The cells were stimulated with hepatocyte growth factor or left at steady state. Following cell lysis, proteins were separated on SDS-PAGE gels and peptides extracted by in-gel trypsinization were analyzed by mass spectrometry. Differentially modulated proteins identified and quantified were subjected to pathway enrichment analysis. In total, 3440 proteins were identified in Hepa cells in the presence of SOCS1 at steady state, of which 181 proteins were significantly modulated by SOCS1. The SH2 domain mutation and HGF stimulation increased the number of differentially modulated proteins, which showed only a limited overlap with SOCS1-modulated proteins. Protein interaction network analysis revealed enrichment of SOCS1-modulated proteins within multiprotein complexes such as ubiquitin conjugating enzymes, proteasome, mRNA spliceosome, mRNA exosome and mitochondrial ribosome. Further analysis indicated SOCS1-dependent regulation of the UBE2D ubiquitin conjugating enzymes, which are implicated in growth factor receptor signaling, indirectly via an unknown protein. Given the ubiquitous and highly regulated induction of SOCS1 by diverse cellular stimuli, our findings suggest a fundamental role of SOCS1 in regulating large macromolecular complexes that are important for cellular homeostasis.
2021-02-01 | PXD019135 | Pride
Project description:To study the role of SOCS1 in the cell nucleus in vivo, we generated a transgenic mouse model using a bacterial artificial chromosome (BAC) containing a mutated Socs1 locus (non-nuclear Socs1ÎNLS), GFP and firefly Luciferase, termed MGL. MGL transgenic mice expressing only non-nuclear mutant Socs1 (Socs1-/- MGLtg mice) survive the early lethal phenotype of Socs1-/- mice that die within 3 weeks due to excessive immune signaling, mainly depending on hyperresponsiveness to IFNgamma. Therefore, we suggested that classical IFNgamma signaling might still be efficiently regulated by SOCS1ÎNLS. To prove this hypothesis, bone marrow-derived macrophages (BMMs) from Socs1-/- MGLtg mice and the control group (Socs1+/- MGLtg mice) were stimulated with IFNgamma for 24 h and subjected to whole-genome expression analysis.
2016-11-10 | E-MTAB-4938 | biostudies-arrayexpress
Project description:In vivo, the expansion of antigen experienced CD4+ T cells is limited by intrinsic factors. Using an in vivo genome-wide CRISPR-Cas9 screen, we identified SOCS1 as a major non-redundant checkpoint imposing a brake on antigen experienced CD4+ T-cell proliferation upon antigen challenge. Although SOCS1 has been previously described as an inhibitor of CD8+ T-cell effector function, we highlight here that it is abrogating the CD4+ T-cell response. SOCS1 integrates several cytokines receptor signals to actively silence TCR-induced polycytokine signaling pathways, restraining CD4+ T cell proliferation and functions. Targeting SOCS1 in mouse and human CD4+ and CD8+ T cells improved the therapeutic efficacy of antitumor adoptive T-cell therapies, enhancing intra-tumor T cell accumulation, persistence and effector functions. SOCS1 deletion in CAR-T cells enhances CD4+ CAR T-cell proliferation/survival and polyfunctionality in vivo, promoting long term rejection of established tumors. These findings identify SOCS1 as a major intracellular checkpoint inhibitor of re-stimulated CD4+ T cells, opening new possibilities to optimize adoptive T cell therapies.
2021-09-02 | GSE154791 | GEO
Project description:Suppressor of cytokine signaling-1 (SOCS1) exerts control over inflammation by targeting p65 NFκB for degradation in addition to its canonical role regulating cytokine signaling. We report here that SOCS1 does not operate on all p65 targets equally, instead localizing to a select subset of pro-inflammatory genes. Promoter-specific interactions of SOCS1 and p65 determine the subset of genes activated by NFκB during systemic inflammation, with profound consequences for cytokine responses, immune cell mobilization, and tissue injury. Nitric oxide synthase-1 (NOS1)-derived NO is required and sufficient for displacement of SOCS1 from chromatin, permitting full transcriptional activation of these genes. Single cell transcriptomic analysis of NOS1-deficient animals led to the detection of a regulatory macrophage subset, which exerts potent suppression on inflammatory cytokine responses and tissue remodeling. These results provide the first example of a redox-sensitive, gene-specific mechanism for converting macrophages from cells that regulate inflammation to cells licensed to promote aggressive and potentially injurious inflammation.
2023-03-01 | GSE225833 | GEO
Project description:Timecourse analysis of Interferon-Gamma (IFNg) signalling in mice deficient for IFNg or both IFNg and Suppressor of Cytokine Signalling-1 (SOCS1). Keywords: time course expression analysis
2006-02-14 | GSE4232 | GEO
Project description: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-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ 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-γ 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-γ 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-γ 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-γ by NK cells.
2022-09-14 | GSE205824 | GEO
Project description: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-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ 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-γ 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-γ 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-γ 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-γ by NK cells.
2022-09-14 | GSE205821 | GEO
Project description:Tumor Infiltrating Lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the anti-tumor activity of T cell therapies, large-scale in vitro and in vivo CRISPR/Cas9 screens were performed, with the suppressor of cytokine signaling 1 (SOCS1) gene identified as a top T cell-enhancing target. In murine CD8 T cell therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of T central memory cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cell (Texprog) cells in tumors. A comprehensive CRISPR tiling screen of the SOCS1 coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with a sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo anti-tumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies.
2023-07-30 | GSE237694 | GEO
Project description:Tumor Infiltrating Lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the anti-tumor activity of T cell therapies, large-scale in vitro and in vivo CRISPR/Cas9 screens were performed, with the suppressor of cytokine signaling 1 (SOCS1) gene identified as a top T cell-enhancing target. In murine CD8 T cell therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of T central memory cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cell (Texprog) cells in tumors. A comprehensive CRISPR tiling screen of the SOCS1 coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with a sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo anti-tumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies.
2023-07-30 | GSE237691 | GEO