Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275375 | ENA |
REPOSITORIES: ENA
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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: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:From mice, strand-specific RNA-Seq of granulocyte-myeloid progenitors (GMP) and hematopoietic stem cells (HSC). Cancer stem cells (CSC) were created with MLL-ENL transfections using puromycin for both GMP and HSCs. Further knock-outs were created of -catenin (Ctnnb1) and Hoxa9.
2017-10-10 | E-MTAB-3647 | biostudies-arrayexpress
Project description:C-di-GMP signaling can directly influence bacterial behavior by affecting the functionality of c-di-GMP-binding proteins. In addition, c-di-GMP can exert an indirect and more global effect on gene transcription or translation, e.g. via riboswitches or by binding to transcription factors. In this study, we investigated the effects of changes in intracellular c-di-GMP levels on gene expression and protein production in the opportunistic pathogen Pseudomonas aeruginosa. We induced c-di-GMP production via an ectopically introduced diguanylate cyclase and recorded the transcriptional, translational as well as proteomic profile of the cells. We demonstrate that rising levels of c-di-GMP in P. aeruginosa under growth conditions otherwise characterized by low c-di-GMP levels immediately cause a switch to a non-motile, auto-aggregative phenotype. This switch became apparent before any c-di-GMP-dependent role on transcription, translation, or protein abundance could be observed. Our results indicate that sudden rises in global c-di-GMP pools affect the P. aeruginosa phenotype via an alteration of protein functionality, rather than an impact on global gene transcription or translation.
2024-09-03 | GSE183394 | GEO
Project description:Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second messenger that coordinates lifestyle transitions, virulence, and developmental processes. In Clostridioides difficile, elevated c-di-GMP levels inhibit sporulation, but the underlying mechanism remained unclear. Here, we identified a conserved family of small, membrane-associated proteins as previously unrecognized effectors of c-di-GMP signaling. Their expression is controlled by class I c-di-GMP-responsive riboswitches. Transcriptomic analyses revealed that c-di-GMP represses these genes, and reporter assays demonstrated riboswitch-dependent transcriptional regulation via premature termination mechanism. Overexpression of a single member, CD1980.2, was sufficient to trigger the transcriptional activation of sporulation genes, including sigma factors and their regulons, and to increase spore formation. Conversely, sporulation efficiency decreased proportionally with the number of deleted small protein genes, and the strain lacking all seven genes displayed a severe sporulation defect, underscoring their cumulative and functionally redundant roles. Elevating c-di-GMP levels in the deletion mutant did not further reduce sporulation, supporting a model in which c-di-GMP inhibits spore formation by repressing the expression of this small-protein family. Our work establishes these small proteins as critical effectors linking c-di-GMP signaling to developmental output in C. difficile. Their redundancy, conservation, and integration into riboswitch- and RgaR-mediated regulatory pathways highlight their central role in spore formation, a process essential for pathogen persistence and transmission. These findings expand the repertoire of second-messenger effectors in bacterial physiology.
2026-08-15 | GSE310232 | GEO
Project description:Shewanella spp. possess a broad respiratory versatility, which contributes to the occupation of hypoxic/anoxic environmental or host-associated niches. Here we observed a strain-specific induction of biofilm formation in response to supplementation with the anaerobic electron acceptors dimethyl sulfoxide (DMSO) and nitrate in a panel of Shewanella algae isolates. The respiration-driven biofilm response is not observed in DMSO and nitrate reductase deletion mutants of the type strain S. algae CECT 5071, and can be restored upon complementation with the corresponding reductase operon(s) but not by an operon containing a catalytically inactive nitrate reductase. The distinct transcriptional changes, proportional to the effect of these compounds on biofilm formation, include cyclic di-GMP (c-di-GMP) turnover genes. In support, ectopic expression of the c-di-GMP phosphodiesterase YhjH of Salmonella Typhimurium but not its catalytically inactive variant decreased biofilm formation. The respiration-dependent biofilm response of S. algae may permit differential colonization of environmental or host niches.
2020-12-05 | GSE133627 | GEO
Project description:Leukemias and other cancers possess a rare population of cells capable of self-renewal, and eradication of these cancer stem cells is likely necessary for long-term cancer-free survival. Given that both normal and cancer stem cells are capable of self-renewal the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. We introduced the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23) found in human acute myelogenous leukemia (AML) into murine committed granulocyte-macrophage progenitors (GMP). The resultant leukemias contained cells with an immunophenotype similar to normal GMP that were highly enriched for leukemia stem cells (LSC). Detailed gene expression comparisons between normal hematopoietic stem cells (HSC), committed progenitors, and the LSC population demonstrated the LSC were globally more similar to the normal GMP than any other population. However, a subset of genes highly expressed in normal stem cells was re-activated in the LSC. These data demonstrate LSC can be generated from committed progenitors without widespread reprogramming of gene expression, and a leukemia self-renewal associated signature is activated in the process. Our findings define progression from normal hematopoietic progenitor to leukemia stem cell, and suggest that targeting a self-renewal program expressed in an abnormal context may be possible. Experiment Overall Design: A normal HSC enriched population, common myeloid progenitors, granulocyte macrophage progenitors, megakaryocyte progenitors, and leukemia stem cells (leukemic-GMP) were isolated and labeled RNA was hybridzed to Affymetrix microarrays
2008-06-12 | E-GEOD-3722 | biostudies-arrayexpress
Project description:Although the ubiquitous bacterial secondary messenger cyclic diguanylate (c-di-GMP) plays important roles in various cellular functions including the formation of biofilm in a wide range of bacteria, its function in model plant pathogen Pseudomonas syringae is largely elusive. In order to test this in P. syringae, we overexpressed a diguanylate cyclase (YedQ) and a phosphodiesterase (YhjH) that are originally from Escherichia coli, resulting in high and low c-di-GMP levels in P. syringae, respectively. Through performing genome-wide RNA sequencing of these two strains, we found that c-di-GMP regulates (i) fliN, fliE and flhA genes, which are associated with flagellar assembly, (ii) alg8 and alg44, which are related to exopolysaccaride biosynthesis pathway, (iii) pvdE, pvdP and pvsA genes, related to siderophore biosynthesis pathway, and (iv) sodA, which is a superoxide dismutase. In particular, we identified five genes sensitive to elevated c-di-GMP level and constructed five luciferase-based reporters that effectively respond to intracellular level of c-di-GMP in P. syringae, which can be used to measure c-di-GMP levels in vivo in the future. Based on the RNA-seq results, phenotypic assays confirmed that c-di-GMP regulated many important biological pathways in P. syringae, such as negative regulation of type III secretion system (T3SS) and motility as well as positive regulation of EPS production, siderophore production and oxidative stress resistance. Taken together, the present study demonstrated that c-di-GMP is closely related to virulence and stress response in P. syringae, suggesting that tuning its level can be a new strategy to protect plants from the attack of this pathogen in the future.
2019-03-31 | GSE120889 | GEO
Project description:The fetal liver (FL) plays a fundamental role in the ontogeny of the hematopoietic system, by transiently providing a fertile microenvironment for the maturation, proliferation and expansion of fetal hematopoietic progenitors, as well as definitive hematopoietic stem cells (HSCs). Nonetheless, the cellular make up and identity of hematopoietic stem and progenitor cell niches in the FL remain underexplored. Here we employed bulk mRNA-seq to investigate the spatiotemporal dynamics and functional relevance of putative niche cells and HSCs in the FL microenvironment. We find that at peak stages of FL hematopoiesis, pro-hematopoietic cytokines are promiscuously expressed by endothelial, mesenchymal cells and hepatoblasts, which form multicellular consortia that collectively provide unrestricted access to supportive factors throughout the entire tissue. Nevertheless, during peak hematopoietic stages, hepatoblasts are most abundant, express highest levels of growth factors and regulate fetal erythropoiesis and HSC expansion through production of Kit ligand. This highly conducive FL microenvironment is transient and gets rapidly remodeled through hepatoblast differentiation, leading to the downregulation of hematopoietic factors and the contraction of supportive niches, which temporarily coincide with the exit of HSCs towards emergent BM tissues.
2025-10-30 | E-MTAB-15617 | biostudies-arrayexpress
Project description:The bacterial second messenger c-di-GMP is known to influence the formation of biofilms and thereby persistence of pathogenic and beneficial bacteria in hosts. A previous evolution experiment with Pseudomonas lurida MYb11, occasional symbiont of the nematode Caenorhabditis elegans, led to the emergence of host-specialized variants with elevated intracellular c-di-GMP. Thus far, the molecular underpinnings of c-di-GMP-mediated host specialization were unknown in this symbiosis. Therefore, the current study aimed at identifying candidate molecular processes by combining transcriptomic and functional genetic analyses. We found that MYb11 host specialists differentially expressed genes related to attachment, motility and biofilm production, including pelD from the pel gene cluster. pelD deletion resulted in reduced intra-host competitive fitness, lower bacterial numbers in C. elegans and loss of biofilm biomass. Our results identify pelD as a previously unknown key modulator of beneficial symbiont-host associations that acts downstream of c-di-GMP.
2025-01-30 | GSE288391 | GEO