Human immature neutrophils as a functional biomarker of systemic vascular pathologies
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA622530 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11465486_1.fastq.gz | Fastqsanger.gz | |||
| SRR11465486_2.fastq.gz | Fastqsanger.gz | |||
| SRR11465487_1.fastq.gz | Fastqsanger.gz | |||
| SRR11465487_2.fastq.gz | Fastqsanger.gz | |||
| SRR11465488_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:We used an ex vivo system of murine ER-Hoxb8 neutrophils that phenotypically and morphologically recapitulate neutrophil maturation stages during five days of in vitro culture in the presence of G-CSF. To investigate the development of the ROS system in neutrophils during their development, we compared transcriptomes of D0, D1, D3 and D5 Hoxb8 neutrophils.
2020-09-15 | GSE147910 | GEO
Project description:Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.
| S-EPMC7605529 | biostudies-literature
Project description:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
2021-10-05 | GSE157789 | GEO
Project description:Neutrophils play a key role in the control of metastatic progression. Neutrophils are phenotypically heterogeneous and can exert either anti- or pro-metastatic functions. Here, we demonstrate that tumor cells capable of forming liver metastases induce an accumulation of neutrophils in the peripheral blood and liver parenchyma. Cancer cell-derived G-CSF, in concert with other factors, mobilizes immature low-density neutrophils that promote liver metastasis. In contrast, mature high-density neutrophils inhibit the formation of liver metastases. Transcriptomic and metabolomic analyses of high- and low- density neutrophils reveal engagement of numerous metabolic pathways specifically in low-density neutrophils. Low-density neutrophils exhibit enhanced global bioenergetic capacity, through their ability to engage mitochondrial-dependent ATP production, and remain capable of executing pro-metastatic neutrophil functions, including NETosis, under nutrient-deprived conditions. Together, these data reveal that distinct pro-metastatic neutrophil populations exhibit a high degree of metabolic flexibility, which facilitates metastatic progression and the formation of liver metastases.
2019-06-26 | GSE123669 | GEO
Project description:Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19
| PRJNA662785 | ENA
Project description:Monocytes and neutrophils are both myeloid cells that have the same progenitor, the granulocyte macrophage precursor (GMP). Neutrophils are mature innate cells that are phagocytes and can degranulate to mount an immune response, whereas monocytes are immature pluripotent cells that can differentiate into macrophages and dendritic cells that can phagocytose and present antigen. To compare the expression pattern and validate samples purity by comparing expression data with previously generated data for monocytes and neutrophils, we isolated monocytes (CD45+ CD64+ CD14+ CD16-) and neutrophils (CD66b+ CD16+) from eight healthy volunteers.
2014-03-20 | E-MTAB-1573 | biostudies-arrayexpress
Project description:Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis
| PRJNA509476 | ENA
Project description:This study used proteomic, biomechanical, and functional analyses to further define neutrophil heterogeneity in the context of SLE. Mass spectrometry proteomic and phosphoproteomic analyses were performed in healthy control normal density neutrophils (NDNs), SLE NDNs and in autologous SLE LDGs. Proteomic and phosphoproteomic differences were detected when comparing control to SLE neutrophils and when comparing SLE NDNs to SLE LDGs.
2021-11-04 | PXD021096 | Pride
Project description:Despite the remarkable success of immunotherapy, only ~20-30% of cancer patients display an extended durable response. Pre-existing biomarkers for immunotherapy outcome are significantly limited in their predictive power. While mice are the most widely used and cost-effective model to study human disease, translating preclinical biomarkers into clinical practice faces significant obstacles – in part due to the lack of diverse or appropriate models. Here, to improve translatability and identify novel biomarkers, we showcase an approach encompassing several pre-clinical models - each capturing one possible mechanistic aspect of immunotherapy response, such as tumor- and host-dependency, in order to reflect the variability seen in human cancers. Using this approach, we identify interferon-stimulated, Ly6Ehi neutrophils as a pre-treatment, blood-borne biomarker for anti-PD1 response in mice. We subsequently validate this result in cohorts of immunotherapy-treated non-small cell lung cancer (NSCLC) and melanoma patients, where the abundance of Ly6Ehi neutrophils predicts anti-PD1 response and further validated these results using available datasets for other cancers. Moreover, we demonstrate that these cells sensitize otherwise resistant tumors to anti-PD1 therapy, in part by directly activating cytotoxic T cells and contributing to tumor cell killing, while operate upstream of T cells in the immunotherapy response. Collectively, our study identifies a new and functionally active biomarker to predict immunotherapy outcome with potential clinical relevance.
2024-01-05 | GSE226962 | GEO
Project description:Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as vascular damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, and can contribute to vascular repair as well as to cardiovascular pathologies such as intimal hyperplasia/restenosis in coronary artery and arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity. UHRF1 expression correlated with the development of vascular pathologies associated with modulation of noncoding RNAs, such as microRNAs. miR-145 — pivotal in regulating VSMC plasticity, which is reduced in vascular diseases — was found to control Uhrf1 mRNA translation. In turn, UHRF1 triggered VSMC proliferation, directly repressing promoters of cell-cycle inhibitor genes (including p21 and p27) and key prodifferentiation genes via the methylation of DNA and histones. Local vascular viral delivery of Uhrf1 shRNAs or Uhrf1 VSMC-specific deletion prevented intimal hyperplasia in mouse carotid artery and decreased vessel damage in a mouse model of aortic aneurysm. Our study demonstrates the fundamental role of Uhrf1 in regulating VSMC phenotype by promoting proliferation and dedifferentiation. UHRF1 targeting may hold therapeutic potential in vascular pathologies.
2018-12-05 | GSE99472 | GEO