Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages

ABSTRACT: Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages

PROVIDER: PRJNA317673 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR3346080.fastq.gz	Fastqsanger.gz
	SRR3346090.fastq.gz	Fastqsanger.gz
	SRR3346100.fastq.gz	Fastqsanger.gz
	SRR3346250_1.fastq.gz	Fastqsanger.gz
	SRR3346250_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 43

Similar Datasets

Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages [RNA-seq]

Project description:Mononuclear phagocytes are a diverse cell family that occupy all tissues and assume numerous functions to support tissue and systemic homeostasis. Our ability to investigate the roles of individual subsets is limited by an absence of approaches to ablate gene function within specific sub-populations. Using Nr4a1-dependent Ly6Clow monocytes as a representative cell type we show that enhancer deletion addresses these limitations. Combining ChIP-Seq and molecular approaches we identify a single, conserved, sub-domain within the Nr4a1 enhancer that is essential for Ly6Clow monocyte development. Mice lacking this enhancer lack Ly6Clow monocytes but retain Nr4a1 gene expression in macrophages during steady state and in response to LPS. Nr4a1 is a key negative regulator of inflammatory gene expression and decoupling these processes allows Ly6Clow monocytes to be studied without confounding influences. Enhancer targeting possesses greater specificity than cre recombinase-mediated gene deletion, providing a route to generate loss-of-function models in closely related cell types.

2016-11-02 | GSE80036 | GEO

Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages [ChIP-seq]

2016-11-02 | GSE80031 | GEO

Triggering of NOD2 receptor converts inflammatory Ly6Chigh into Ly6Clow monocytes with patrolling properties.

Project description:In the present study, we demonstrate that NOD2 receptor triggering by muramyl dipeptide converts blood inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Muramyl dipeptide administration to Nr4a1-/- mice, which lack Ly6Clow monocytes, and to Ly6Clow-depleted mice leads to the emergence of blood patrolling monocytes expressing phenotypic profile of typical Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Furthermore using intravital microscopy in live animal models of inflammatory diseases, we observed that converted Ly6Chigh monocytes are capable of patrolling the endothelium of blood vessels and their presence contributes to reduce the inflammatory response following muramyl dipeptide injection.

2019-01-14 | GSE101496 | GEO

Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-11-02 | GSE80040 | GEO

Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

Project description:The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes. Though sustained hyper-O-GlcNAcylation aggravates pathogenesis of many chronic diseases, accumulating evidence also indicates that acute augmentation in O-GlcNAcylation seems to benefit disease healing in some cases. Glucosamine (GlcN) is a freely available and commonly used dietary supplement for human cartilage health, which also activates the hexosamine biosynthesis pathway and induces protein O-GlcNAcylation. Here we show that both GlcN early and late therapies effectively facilitate cardiac recovery in mice by elevating accumulation of Ly6Clow Mo/Mps in infarcted hearts. Eliminating Mo/Mps with clodronate liposomes fully abolishes aforementioned cardiac healing role of GlcN. Importantly, GlcN supplementation accelerates not only in vitro mobility of reparative Mo/Mps but also in vivo infiltration of Ly6Clow Mos. Mechanistically, GlcN positively regulates transcription of myeloid CX3C chemokine receptor 1 (Cx3cr1) by improving STAT1 O-GlcNAcylation, which stabilizes STAT1 and subsequently promotes chemotaxis and infiltration of Ly6Clow Mos. In summary, we identify a novel anti-inflammatory role of GlcN and suggest that its protective effects are mediated through chemotaxis of Ly6Clow Mos in a STAT1/CX3CR1-dependent fashion, which is controlled by O-GlcNAcylation of STAT1. Our study provides a novel clue for Mo/Mps modulator therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.

2022-04-06 | GSE193613 | GEO

Mus musculus

Project description:Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages [ChIP-seq]

| PRJNA317669 | ENA

Mus musculus

Project description:Targeted deletion of an Nr4a1 associated enhancer ablates Ly6Clow monocytes while protecting pleiotropic gene function in macrophages [RNA-seq]

| PRJNA317674 | ENA

Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

Project description:Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

| PRJNA796947 | ENA

Retinal Ly6Clow Mo/MΦ protect optic nerve against injury

Project description:We investigate the therapeutic effect of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs), a potent immune-modulating therapy for tissue regeneration, in repairing optic nerve damage. Intraocular administration of MSC-sEVs promotes both RGC survival and axon regeneration against optic nerve crush injury. Mechanistically, MSC-sEVs recruits a neural restorative population of hematogenous Ly6Clow monocyte/monocyte-derived macrophage (Mo/MΦ). Gain-of-function by intravitreal administration of the donor Ly6Clow Mo/MΦ markedly improves neurological outcomes in vivo. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.

2024-02-21 | GSE223529 | GEO

CCN1/CYR61-mediated meticulous patrolling by Ly6Clow monocytes fuels vascular inflammation.

Project description:Inflammation is characterized by the recruitment of leukocytes from the bloodstream. The rapid arrival of neutrophils is followed by a wave of inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. In contrast Ly6C(low) monocytes survey the endothelium in the steady state, but their role in inflammation is still unclear. Here, using confocal intravital microscopy, we show that upon Toll-like receptor 7/8 (TLR7/8)-mediated inflammation of mesenteric veins, platelet activation drives the rapid mobilization of Ly6C(low) monocytes to the luminal side of the endothelium. After repeatedly interacting with platelets, Ly6C(low) monocytes commit to a meticulous patrolling of the endothelial wall and orchestrate the subsequent arrival and extravasation of neutrophils through the production of proinflammatory cytokines and chemokines. At a molecular level, we show that cysteine-rich protein 61 (CYR61)/CYR61 connective tissue growth factor nephroblastoma overexpressed 1 (CCN1) protein is released by activated platelets and enables the recruitment of Ly6C(low) monocytes upon vascular inflammation. In addition endothelium-bound CCN1 sustains the adequate patrolling of Ly6C(low) monocytes both in the steady state and under inflammatory conditions. Blocking CCN1 or platelets with specific antibodies impaired the early arrival of Ly6C(low) monocytes and abolished the recruitment of neutrophils. These results refine the leukocyte recruitment cascade model by introducing endothelium-bound CCN1 as an inflammation mediator and by demonstrating a role for platelets and patrolling Ly6C(low) monocytes in acute vascular inflammation.

| S-EPMC4995973 | biostudies-literature