Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcript expression analysis of the NETotic neutrphils

ABSTRACT: Neutrophils are short-lived innate immune cells. Upon encountering appropriate stimuli, neutrophils generate and release neutrophil extracellular traps (NETs), primarily via NADPH oxidase (Nox)-dependent (~2 hours) or Nox-independent NETosis (~15-60 minutes). Ironically, DNA transcription in dying neutrophils remains an enigma. We hypothesized that transcriptional activation, regulated by NETosis-specific kinases, is important to drive the chromatin decondensation necessary for NETosis. For the first time, we show here that (i) the degree of NETosis corresponds to the degree of genome-wide transcription; (ii) kinase-specific transcriptional activation reflects transcriptional firing during different types of NETosis; and (iii) Transcriptomics suggests that NETosis could differentially regulate inflammation. Therefore, we propose that the initial steps of transcriptional firing, but neither transcription per se help to drive NETosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80489 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA319047

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Transcriptome sequencing of human neutrophil

Project description:TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. In situ NETosis of kidneys from pyelonephritis mouse model induced by TcpC-secreting wild-type CFT073 (CFT073wt) and LPS-induced in vitro NETosis in CFT073wt- or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses suggest that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.

2021-05-05 | GSE173807 | GEO

RNA sequencing of primary Sjögren’s syndrome neutrophils

Project description:Objective Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases, however, their roles in primary Sjögren’s syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in this study. Methods pSS patients were enrolled according to the corresponding diagnostic criteria. NETosis markers were measured in plasma and small salivary gland using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (mitoROS) production and JC-1 was measured by flow cytometry. Results NETosis markers including cell free-DNA (cf-DNA), myeloperoxidase (MPO) in plasma and small salivary gland from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated Type I IFN signaling pathway and higher expression of type I interferon related genes in pSS neutrophils. Further stimulating with IFN-α 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils. Conclusions Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.

2022-01-25 | GSE194234 | GEO

Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis

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

BROAD TRANSCRIPTIONAL FIRING REPRESSES BACTERICIDAL ACTIVITY IN HUMAN AIRWAY NEUTROPHILS

Project description:BROAD TRANSCRIPTIONAL FIRING REPRESSES BACTERICIDAL ACTIVITY IN HUMAN AIRWAY NEUTROPHILS

| PRJNA693842 | ENA

Broad transcriptional firing represses bactericidal activity in human airway neutrophils

Project description:Broad transcriptional firing represses bactericidal activity in human airway neutrophils

| PRJNA702818 | ENA

Broad transcriptional firing represses bactericidal activity in human airway neutrophils [Transcriptional_Blockage_CFASN_Neutrophils]

Project description:Broad transcriptional firing represses bactericidal activity in human airway neutrophils [Transcriptional_Blockage_CFASN_Neutrophils]

| PRJNA702815 | ENA

Broad transcriptional firing represses bactericidal activity in human airway neutrophils [10hours_transmigrated_CFASN_Neutrophils]

Project description:Broad transcriptional firing represses bactericidal activity in human airway neutrophils [10hours_transmigrated_CFASN_Neutrophils]

| PRJNA702819 | ENA

Early and late processes driving NET formation, and the autocrine/paracrine role of endogenous RAGE ligands

Project description:Neutrophil extracellular trap (NET) formation has emerged as an important response against various pathogens; it also plays a role in chronic inflammation, autoimmunity, and cancer. Despite a growing understanding of the mechanisms underlying NET formation, much remains to be elucidated. We previously showed that in human neutrophils activated with different classes of physiological stimuli, NET formation features both early and late events that are controlled by discrete signaling pathways. However, the nature of these events has remained elusive. We now report that PAD4 inhibition only affects the early phase of NETosis, as do distinct signaling intermediates (TAK1, MEK, p38 MAPK). Accordingly, the inducible citrullination of residue R2 on histone H3 is an early neutrophil response that is regulated by these kinases; other arginine residues on histones H3 and H4 do not seem to be citrullinated. Conversely, chromatin decondensation is a belated event in NET formation, that is impaired by the inhibition of most signaling pathways known to control the phenomenon. We additionally show that neutrophils can condition themselves to be poised for rapid NET formation, and that this represents another late process. Similarly, activated neutrophils release a number of endogenous proteic factors that promote and largely mediate NET generation, and this is yet another late process. Our data shed new light on the cellular processes underlying NET formation, and unveil some unsuspected facets of the phenomenon. In view of the involvement of NETs in both homeostasis and several pathologies, our findings are of broad relevance.

2021-10-12 | PXD027055 | Pride

Tamm-Horsfall protein augments neutrophil NETosis

Project description:Proteome profiles of isolated peripheral human neutrophils pretreated with purified Tamm-Horsfall protein and stimulated to undergo NETosis with PMA.

2024-09-23 | PXD045468 | Pride

Human lupus netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules

Project description:Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-?. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients. Human neutrophils and LDGs were isolated from PBMCs. RNA from healthy neutrophils, lupus neutrophils and lupus LDGs was extracted and processed for hybridization on Affymetrix microarrays.

2011-06-22 | E-GEOD-26975 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data