Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1140315 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR30000672_1.fastq.gz | Fastqsanger.gz | |||
| SRR30000672_2.fastq.gz | Fastqsanger.gz | |||
| SRR30000679_1.fastq.gz | Fastqsanger.gz | |||
| SRR30000679_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:Single cell transcriptome profiling illuminates conserved anti-bacterial neutrophil state evoked by IFNr signaling
| PRJNA1139401 | ENA
Project description:Single-Cell Transcriptome Profiling Reveals Conserved IFNr-IL8 Signaling-Induced Antibacterial Neutrophil States during Bacterial Infection (PRJCA044405)
| PRJDB39107 | ENA
Project description:Neutrophils rapidly respond to inflammation and infection, but to which degree their functional trajectories after mobilization from the bone marrow can be shaped within the circulation remains vague. Phenotypic changes of circulating neutrophils caused by systemic inflammation are thought to result from several factors, including a “left shift” of the neutrophil compartment towards younger bone marrow-derived subsets. However, experimental limitations have so far hampered neutrophil research in human disease. Here, using innovative fixation and single-cell-based toolsets, we profile the human and murine neutrophil transcriptome and proteome during steady state and bacterial infection. We find that peripheral priming of circulating neutrophils leads to plastic shifts dominated by conserved upregulation of antimicrobial genes across neutrophil substates, facilitating pathogen containment. We show the TLR4/NF-κB-signaling dependent upregulation of canonical neutrophil activation markers like CD177/NB-1 during acute inflammation, resulting in functional shifts in vivo. Importantly, blocking de novo RNA synthesis in circulating neutrophils abrogates these plastic shifts and prevents the adaptation of antibacterial neutrophil programs by upregulation of distinct effector molecules upon infection. In summary, these data underline transcriptional plasticity as a relevant mechanism of functional neutrophil reprogramming during acute infection to foster bacterial containment within the circulation. This adds to the understanding of competing modes of adaptation to inflammatory challenges by the neutrophil compartment.
2024-05-21 | PXD048335 | Pride
Project description:The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here we profiled more than 25,000 mouse differentiating and mature neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function, and fate decision in their steady state and during bacterial infection. Eight neutrophil populations (including the GMP population) were defined by distinct molecular signatures, including a new circulating mature neutrophil population highly expressing interferon-stimulated genes. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets, a novel mechanism that highlights the complex and precise regulation of neutrophil production. Neutrophil heterogeneity and differentiation are driven by both known and uncharacterized transcription factors. Neutrophils gradually acquire microbicidal capability as cells traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil population, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall heterogeneity. Bacterial infection-induced emergency granulopoiesis is mediated by augmented proliferation of early-stage neutrophil progenitors and accelerated post-mitotic maturation. In summary, single-cell transcriptomics enabled the reconstruction of neutrophil differentiation and maturation trajectories and uncovered neutrophil subpopulations, gene pathways, and regulators of neutrophil function and fate decisions. These data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers, and therapeutic targets at single-cell resolution.
2020-05-27 | GSE137539 | GEO
Project description:Despite durable remissions observed in a subset of cancer patients treated with immunotherapy, the majority remain unresponsive, underscoring the need for predictive biomarkers and novel therapeutic targets. In this study, we integrated single-cell RNA sequencing, spatial transcriptomics, and conditional knockout mouse models to uncover a conserved neutrophil interferon (IFN)-stimulated gene signature that predicts responsiveness to anti-PD1 therapy. We demonstrate that early reductions in neutrophil abundance and neutrophil IFN responses are strongly associated with therapeutic efficacy, while the spatial exclusion of neutrophils from tertiary lymphoid structures emerges as a hallmark of successful treatment. Furthermore, our findings reveal that neutrophil IFN signaling is pivotal in mediating resistance to therapy and in impairing the development of durable immunological memory. These findings offer insights into the interplay between neutrophil IFN signaling and adaptive immunity, providing a foundation for developing bloodborne biomarkers and combinatorial strategies to enhance the efficacy of immune checkpoint blockade therapy.
2026-05-22 | GSE301336 | GEO
Project description:In mammals, the cGAS-cGAMP-STING pathway is crucial for sensing viral infection and initiating an anti-viral type I interferon response. cGAS and STING are highly conserved genes that originated in bacteria and are present in most animals. By contrast, interferons only emerged in vertebrates; thus, the function of STING in invertebrates is unclear. Here, we use the STING ligand 2'3'-cGAMP to activate immune responses in a model cnidarian invertebrate, the starlet sea anemone Nematostella vectensis. Using RNA-Seq, we found that 2'3'-cGAMP induces robust transcription of both anti-viral and anti-bacterial genes, including the conserved transcription factor NF-κB. Knockdown experiments identified a role for NF-κB in specifically inducing anti-bacterial genes downstream of 2'3'-cGAMP, and some of these genes were also found to be induced during Pseudomonas aeruginosa infection. Furthermore, we characterized the protein product of one of the putative anti-bacterial genes, the N. vectensis homolog of Dae4, and found that it has conserved anti-bacterial activity. This work describes an unexpected role of a cGAMP sensing pathway in anti-bacterial immunity and suggests that a broad transcriptional response is an evolutionarily ancestral output of 2'3'-cGAMP signaling in animals.
2021-06-03 | GSE175984 | GEO
Project description:The omentum, a visceral adipose tissue with critical metabolic, immunological, and stem cell functions is the preferred site for ovarian cancer metastasis. However, its role in maintaining homeostasis and its responses to metastatic colonization remain incompletely understood. Using single-cell transcriptomics, we profiled different anatomical regions of the omentum in patients with benign conditions and ovarian cancer metastasis. We cataloged the benign omentum and found stable cell type composition and preservation of a stem and progenitor niche. Upon metastatic colonization, the immune landscape diversified accompanied by a gradual loss of mesothelial and progenitor cells. The lesser omentum, which is not routinely removed during surgical debulking, was identified as a premetastatic niche characterized by neutrophil infiltration, NETosis, and the presence of micrometastases. At established metastatic sites, resident cells exhibited cancer-associated phenotypes with regulatory, anti-adipogenic, and immunosuppressive functions. Cancer cells orchestrated the cell reprogramming via a repertoire of signaling factors affecting both proximal and distal omental tissue. This cell atlas illuminates the cellular and molecular determinants of organ homeostasis and reveals a high degree of plasticity and cellular reprogramming promoted by cancer colonization.
2024-11-07 | MSV000096327 | MassIVE
Project description:Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response, S. aureus can cause persistent infection. Here we demonstrate that S. aureus impairs neutrophil function by triggering the production of the anti-inflammatory metabolite, itaconate. The enzyme that synthesizes itaconate, Irg1, is selectively expressed in neutrophils during S. aureus pneumonia. Itaconate inhibits neutrophil glycolysis and oxidative burst, which impairs survival and bacterial killing. In a murine pneumonia model, neutrophil Irg1 expression protects critical lung cell populations from oxidative stress but compromises bacterial clearance. S. aureus is thus able to evade innate immune clearance by targeting neutrophil metabolism and inducing the production of the antiinflammatory metabolite itaconate.
2023-01-01 | GSE215195 | GEO
Project description:Hereditary hemochromatosis (HH) increases susceptibility to bacterial infections, often leading to sepsis, but underlying mechanisms are unclear. Here, we show that HH mice infected with a hyper–yersiniabactin-producing Yersinia pseudotuberculosis Δfur mutant (Δfur) rapidly develop sepsis, marked by an influx of immature, pro-inflammatory CD101⁻ neutrophils with impaired bacterial killing and enhanced NETosis, unlike mature CD101⁺ neutrophils in wild-type mice. We further demonstrate that type I interferon (IFN-I) signaling impairs neutrophil bactericidal function, increasing bacterial burden and driving emergency granulopoiesis in HH mice, in turn which results in systemic recruitment of immature CD101⁻ neutrophils. Blocking IFNAR signaling restores neutrophil function, reduces bacterial loads, limits neutrophil recruitment, and promotes a shift toward mature CD101⁺ neutrophils, ultimately reducing sepsis severity and improving survival. These findings reveal a pathogenic role for immature CD101⁻ neutrophils in driving sepsis and identify IFN-I signaling as a key regulator of this dysfunctional immune response in HH.
2026-05-26 | GSE300863 | GEO
Project description:Porphyromonas gingivalis is a keystone oral pathogen that successfully manipulates the human innate immune defenses, resulting in a chronic pro-inflammatory state of periodontal tissues and beyond. Here we demonstrate that secreted outer membrane vesicles (OMVs) are deployed by P. gingivalis to selectively coat and activate human neutrophils, thereby provoking degranulation without neutrophil killing. Secreted granule components with antibacterial activity, especially LL-37 and MPO, are subsequently degraded by potent OMV-bound proteases known as gingipains, thereby ensuring bacterial survival. In contrast to neutrophils, the P. gingivalis OMVs are efficiently internalized by macrophages and epithelial cells. Importantly, we show that neutrophil coating is a conserved feature displayed by OMVs of at least one other oral pathogen, namely Aggregatibacter actinomycetemcomitans. Altogether, we conclude that P. gingivalis deploys its OMVs for a neutrophil-deceptive strategy to escape phagocytosis and to create a favorable inflammatory niche.
2022-08-16 | PXD026704 | Pride