Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA217916 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional mechanisms that drive angiogenesis and organotypic endothelial specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors. Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent VE-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this transcription factor. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of ß-catenin-dependent genes such as TCF/LEF1 and ZIC3 transcription factors, transporters and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 transcriptional factor gradient and enables organotypic endothelial specialization of the vascular network.
2019-12-05 | GSE141440 | GEO
Project description:Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism in the regulation of macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.
2021-07-30 | GSE179066 | GEO
Project description:The polarization and activation of macrophages are controlled synergistically by transcription factors such as NF-κB and AP-1 transcription factor members. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activity. To determine the full profile of c-Jun network, microarray RNA expression analysis using Agilent Technologies platform was performed in wild-type and c-JunΔLysM macrophages.
2018-10-31 | GSE88898 | GEO
Project description:Here we identify the activator protein-1 (AP-1) factor JunB as an essential regulator of Th17 cell identity. JunB activates the expression of Th17 lineage-specifying genes, and coordinately represses genes controlling Th1 and Treg fate. Through regulatory analysis, we find that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T cell potential.
2017-06-17 | GSE98413 | GEO
Project description:Here we identify the activator protein-1 (AP-1) factor JunB as an essential regulator of Th17 cell identity. JunB activates the expression of Th17 lineage-specifying genes, and coordinately represses genes controlling Th1 and Treg fate. Through regulatory analysis, we find that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T cell potential.
2017-06-17 | GSE98412 | GEO
Project description:The polarization and activation of macrophages are controlled synergistically by transcription factors such as NF-κB and AP-1 transcription factor members. Surprisingly, little is known about the role of the Fra proteins, both members of the AP-1 transcription factor family, in macrophage activity. To determine the full profile of Fra network, microarray RNA expression analysis using Agilent Technologies platform was performed in wild-type, Fra-1ΔMxCre or Fra-2ΔLysMCre macrophages.
2021-05-17 | GSE128787 | GEO
Project description:Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development. Junb-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORt and ROR and reduced expression of Foxp3, a transcription factor known to antagonize RORt function.
2018-02-15 | GSE98242 | GEO
Project description:Tumor associated macrophages show signs of both, classical pro-inflammatory as well as alternative macrophage activation. The aim of this study was to compare TAMs across tumor types, to characterize their phenotype in detail and to identify the signaling nodules involved regulating classical and alternative activation traits.
2015-04-28 | GSE59047 | GEO
Project description:Background: Macrophage polarization programs, commonly referred to as âclassicalâ and âalternativeâ activation, are widely considered as distinct states that are exclusive of one another, and are associated with different functions such as inflammation and wound healing, respectively. In a number of disease contexts, such as traumatic brain injury (TBI), macrophage polarization influences the extent of pathogenesis, and efforts are underway to eliminate pathogenic subsets. However, previous studies have not distinguished whether the simultaneous presence of both classical and alternative activation signatures represents the admixture of differentially polarized macrophages, or if they have adopted a unique state characterized by components of both classical and alternative activation. Results: We analyzed the polarization of individual macrophages responding to TBI using single-cell RNA sequencing. Analysis of signature polarization genes revealed diverse activation states, including M(IL4), M(IL10), and M(LPS, IFNγ). However, the expression of a given polarization marker was no more likely than at random to predict simultaneous expression or repression of markers of another polarization program within the same cell, suggesting a lack of exclusivity in macrophage polarization states in vivo in TBI. Also unexpectedly, individual TBI macrophages simultaneously expressed high levels of signature polarization genes across two or three different polarization states, and in several distinct and seemingly incompatible combinations. Conclusions: Single-cell gene expression profiling demonstrated that monocytic macrophages in TBI are not comprised of distinctly polarized subsets, but are uniquely and broadly activated. TBI macrophage activation in vivo is deeply complex, with individual cells concurrently adopting both inflammatory and reparative features. These data provide physiologically relevant evidence that the early macrophage response to TBI is comprised of novel activation states that are discordant with the current paradigm of macrophage polarizationâa key consideration for therapeutic modulation. Monocyte derived macrophages were isolated from the ipsilateral hemisphere of mouse brains one day following traumatic brain injury elicited by control cortical impact in C57BL/6 adult male mice. Single-cells were isolated and processed for RNA sequencing using a Fluidigm C1 integrated fluidic circuit chip. 45 biological replicates were analyzed.
2016-05-17 | E-GEOD-79510 | biostudies-arrayexpress
Project description:This model is based on the publication:
"Mathematical Modelling of Alternative Pathway of Complement System".
Suruchi Bakshi, Fraser Cunningham, Eva-Maria Nichols, Marta Biedzka-Sarek, Jessica Neisen, Sebastien Petit-Frere, Christina Bessant, Loveleena Bansal, Lambertus A Peletier, Stefano Zamuner, Piet H van der Graaf
DOI: 10.1007/s11538-020-00708-z
Comment:
This model is based on the truncated minimal model equations (Eq. B.1) from the manuscript, which simulate depletion of factor H.
Abstract:
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
2024-09-02 | BIOMD0000001017 | BioModels