Cyclic di-GMP Suppresses Cancer Metastasis by Targeting PSMD3 independently of STING
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE309627 | GEO | 2025/12/19
REPOSITORIES: GEO
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Project description:Cyclic di-GMP Suppresses Cancer Metastasis by Targeting PSMD3 independently of STING
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Project description:Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs) migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns (PAMPs) reportedly mediate HSPC activation, how HSPCs detect pathogen invasion in vivo remains elusive. Bacteria use the second messenger bis-(3’-5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) for a variety of activities. Here we report that c-di-GMP comprehensively regulates both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs, while decreasing the number and repopulation capacity of long-term hematopoietic stem cells (LT-HSCs). Furthermore, we show that type I IFN acts as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while TGF-β1 is required for c-di-GMP-dependent splenic HSPC expansion. Our results define novel machinery underlying dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling. Ten-week-old mice were intraperitoneally administered PBS or 200 nmol c-di-GMP, and CD150+ CD41- CD48- CD34- Flt3- LSK cells of pooled bone marrow from 10 mice per group were sorted 3 days later. mRNA was then extracted using RNeasy micro (Qiagen). Likewise, CD45- Ter-119- CD31- CD140a+ CD51+ MSCs and CD45- Ter119- CD31+ endothelial cells from c-di-GMP-treated or untreated mice were sorted and mRNA was extracted. cDNA was synthesized from mRNA and hybridized to gene chip Mouse60k (Agilent Technologies) and expression levels analyzed.
2015-02-13 | E-GEOD-65905 | biostudies-arrayexpress
Project description:Cyclic di-GMP (c-di-GMP) is a ubiquitous second messenger that regulates many biological processes in bacteria. The genome in Mycobacterium tuberculosis encodes a single copy of the diguanylate cyclase gene (dgc) responsible for c-di-GMP synthesis. To determine the role of c-di-GMP signaling in M. tuberculosis, the mutant strain of Δdgc was generated in the virulent H37Rv strain. We used whole genome microarray expression profiling as a discovery platform to identify the genes controlled by c-di-GMP in M. tuberculosis, providing molecular proof for the phenotypes modulated by the signaling.
2013-10-09 | GSE37973 | GEO
Project description:Cyclic di-GMP Regulates Shigella flexneri Pathogenesis
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Project description:Cyclic di-GMP (c-di-GMP) is a ubiquitous second messenger that regulates many biological processes in bacteria. The genome in Mycobacterium tuberculosis encodes a single copy of the diguanylate cyclase gene (dgc) responsible for c-di-GMP synthesis. To determine the role of c-di-GMP signaling in M. tuberculosis, the mutant strain of Δdgc was generated in the virulent H37Rv strain. We used whole genome microarray expression profiling as a discovery platform to identify the genes controlled by c-di-GMP in M. tuberculosis, providing molecular proof for the phenotypes modulated by the signaling. Wild-type H37Rv and Δdgc cultures were analyzed under aerobic conditions or in an in vitro dormancy model. Bacteria were collected at OD600 =1.3 for the aerobic cultures and upon the beginning of anaerobiosis for the cultures in the dormancy model. One culture for each experiment was assayed except for Δdgc under anaerobiosis (2 independent cultures).
2013-10-09 | E-GEOD-37973 | biostudies-arrayexpress
Project description:Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs) migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns (PAMPs) reportedly mediate HSPC activation, how HSPCs detect pathogen invasion in vivo remains elusive. Bacteria use the second messenger bis-(3’-5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) for a variety of activities. Here we report that c-di-GMP comprehensively regulates both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs, while decreasing the number and repopulation capacity of long-term hematopoietic stem cells (LT-HSCs). Furthermore, we show that type I IFN acts as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while TGF-β1 is required for c-di-GMP-dependent splenic HSPC expansion. Our results define novel machinery underlying dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling.
2015-02-13 | GSE65905 | GEO
Project description:The profiles of transcripts from the V. vulnificus grown under normal and high c-di-GMP conditions were compared by using a V. vulnificus whole-genome microarray Two-condition experiment, normal c-di-GMP condition vs. high c-di-GMP condition. Biological replicates: 3 control, 3 experimental, independently grown and harvested. One replicate per array. For transcriptome analysis, the V. vulnificus whole genome TwinChip, manufactured and kindly provided by the 21C Frontier Microbial Genomics and Applications Center (Daejeon, South Korea), was used.
2013-10-22 | E-GEOD-51459 | biostudies-arrayexpress
Project description:The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. Here we provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by cyclic-di- GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, NF-!B and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways.Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. Three-condition experiment: macrophages transfected with mono-GMP (negative control), double-stranded DNA (positive control), or cyclic-di-GMP (experimental condition). Biological replicates: two, independently treated, harvested, and hybridized to arrays. One replicate per array, except two technical replicates were performed for one of the positive control samples.
2009-07-21 | E-GEOD-16943 | biostudies-arrayexpress
Project description:The cyanobacterial phytochrome Cph2 is a light-dependent diguanylate cyclase producing the second messenger c-di-GMP. Under blue light, the Cph2-dependent increase in the cellular c-di-GMP concentration leads to inhibition of motility in the cyanobacterium Synechocystis 6803. However, the targets of c-di-GMP in this cyanobacterium and its mechanism of action remained unclear. Here, we determined the cellular concentrations of three cyclic nucleotides in wild-type and Δcph2 cells after blue- and green light illumination. Inactivation of the photoreceptor gene completely abolished the blue-light dependent increase in the c-di-GMP content. Microarray analysis revealed that in the wild type in comparison to the Δcph2 mutant, blue light mainly led to a change in accumulation of mRNAs encoding minor pilins, putative chaperone usher pili as well as several chemotaxis regulators. The mRNA encoding the minor pilins pilA5-pilA6 is negatively affected by high c-di GMP content under blue light, whereas the minor pilin encoding operon pilA9-slr2018 accumulates under the same conditions, suggesting opposing functions of the respective gene sets. Based on mutational and gene expression analysis, we further suggest that the second Synechocystis 6803 homolog of a CRP-like transcription factor, SyCRP2, is the regulator of minor pilin gene expression and of putative chaperone usher pili genes slr1667/slr1668. Thus, our work indicates that the Cph2-mediated increase in cellular c-di-GMP concentration upon blue-light illumination specifically changes the transcriptome of Synechocystis 6803.
2020-03-23 | GSE116409 | GEO
Project description:Transcriptomic analysis used to understand the influence of elevated intracellular cyclic-di-GMP in Shewanella oneidensis on expression of c-type cytochrome at transcript level.
2021-01-26 | GSE138586 | GEO