Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

R406-Inhibition of Syk-Cn-NFAT Signaling Axis Promotes Chemical Reprogramming via Metabolic Rewiring and H2S Production

ABSTRACT: R406-Inhibition of Syk-Cn-NFAT Signaling Axis Promotes Chemical Reprogramming via Metabolic Rewiring and H2S Production

PROVIDER: PRJNA647201 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12264870_1.fastq.gz	Fastqsanger.gz
	SRR12264870_2.fastq.gz	Fastqsanger.gz
	SRR12264871_1.fastq.gz	Fastqsanger.gz
	SRR12264871_2.fastq.gz	Fastqsanger.gz
	SRR12264872_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 14

Similar Datasets

R406-Inhibition of Syk-Cn-NFAT Signaling Axis Promotes Chemical Reprogramming via Metabolic Rewiring and H2S Production

Project description:Small molecules not only are convenient and useful for controlling cell fates, but also can provide better understanding of the molecular mechanisms of cell-fate transitions. Here, we identified that spleen tyrosine kinase (Syk) inhibitor R406 could significantly promote the early stage of mouse chemical reprogramming. Furthermore, R406 alleviated the Syk-calcineurin (Cn)-nuclear factor of activated T cells (NFAT) signaling cascade-mediated suppression of glycine, serine and threonine metabolic genes transcriptionally, which is previously unrecognized. In turn, R406 upregulated metabolites of glycine, serine and threonine metabolism and downstream transsulfuration cysteine biosynthesis pathway and cysteine metabolism. Subsequently, increased cellular hydrogen sulfide (H2S) after R406 treatment downregulated oxidative phosphorylation (OXPHOS) and reactive oxygen species (ROS), modulated redox homeostasis, and significantly enhanced chemical reprogramming. In sum, our studies have not only improved the chemical reprogramming technique, but also identified interesting molecular mechanisms of chemical-induced pluripotent reprogramming, which hold great potentials in regenerative medicine.

2021-03-14 | GSE154687 | GEO

NFAT signalling in human mesenchymal stromal cells affects extracellular matrix metabolism and anti-fungal immune responses

Project description:Mesenchymal stromal cells (MSCs) combined with calcineurin-NFAT (CN-NFAT) inhibitors are being tested as a treatment for graft versus host disease (GvHD). The immunosuppressive properties of MSCs seem beneficial; however, their response during fungal infection, which is an important cause of mortality in GvHD patients, is unknown. We report that MSCs phagocytose the fungal component zymosan, resulting in phosphorylation of Syk kinase, increase in cytosolic calcium levels and ultimately, in NFAT1 nuclear translocation. RNA-sequencing analysis of zymosan-treated MSCs showed that CN-NFAT inhibition affects extracellular matrix (ECM) genes, but not cytokine expression that is under the control of the NF-κB pathway. When co-culturing MSCs or decellularized MSC-ECM with human peripheral blood mononuclear cells (PBMCs), selective NFAT inhibition in MSCs decreased cytokine expression by PBMCs. These findings reveal a dual mechanism underlying the MSC response to zymosan: while NF-κB directly controls inflammatory cytokine expression, NFAT impacts immune-cell functions by regulating ECM remodelling.

2021-06-14 | GSE157981 | GEO

Calcineurin-NFAT signaling controls the neutrophils´ ability of chemoattraction upon fungal infection.

Project description:Calcineurin-nuclear factor of activated T-cell (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression but besides their required T-cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitors-treated patients to opportunistic fungal infections. Neutrophils play a crucial role in the innate immunity pathogen defense, while however the effect of CN-NFAT inhibitors on neutrophil function is poorly described. Thus, we tested the response of human neutrophils to fungal pathogens, namely Candida albicans and Aspergillus fumigatus in the presence of CN-NFAT inhibitors. We report that the NFAT pathway members are expressed in neutrophils and mediates part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes. Importantly, genes involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2 , CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.

2024-05-21 | GSE259282 | GEO

Herminiimonas sp. CN strain:CN

Project description:Herminiimonas sp. CN strain:CN Genome sequencing and assembly

| PRJNA209422 | ENA

Hydrogen sulfide (H2S) modulates lifespan of C.elegans

Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated.

2013-07-30 | GSE16975 | GEO

Epigenetic bookmarking of H2S exposure in Caenorhabditis elegans

Project description:Physiological memories of environmental stress can serve to predict future environmental changes, allowing the organism to initiate protective mechanisms and survive. Although physiological memories, or bookmarks, of environmental stress have been described in a wide range of organisms, from bacteria to plants to humans, the mechanism by which these memories persist in the absence of stress is still largely unknown. We have discovered that C. elegans transiently exposed to low doses of hydrogen sulfide (H2S) survive subsequent exposure to otherwise lethal H2S concentrations and induce H2S-responsive transcripts more robustly than naïve controls. H2S bookmarking can occur at any developmental stage and persists through cell divisions and development but is erased by fasting. We show that maintenance of the H2S bookmark requires the SET-2 histone methyltransferase and the CoREST-like demethylase complex. We propose a model in which exposure to low doses of H2S generates a long-lasting, epigenetic memory by modulating H3K4me2 modifications at specific promoters. Understanding the fundamental aspects of H2S bookmarking in this tractable system can provide mechanistic insight into how environmental exposures are translated into the epigenetic landscape in animals.

2019-05-09 | GSE130907 | GEO

RNA-Seq to identify genes expressed by islets in response to metabolic and inflammatory stress and the role of CN/NFAT signaling in this response

Project description:To identify genes expressed in islets in response to metabolic and inflammatory stress, we performed total RNA-Seq on isolated human islets exposed to IL-1β in the presence of high glucose. Gene ontology (GO) analysis of upregulated transcripts indicated enrichment of genes associated with cytokine signaling and proinflammatory responses. Multiple cytokines and chemokines were induced, and several key regulators of oxidative and ER stress responses were upregulated. The results revealed acute induction of proinflammatory transcripts and upregulation of genes involved in oxidative and ER stress in human islets in response to IL-1β and high glucose. Blockade of CN/NFAT signaling by FK506 pretreatment resulted in suppression of genes required for islet cell differentiation, development, and function.

2022-03-01 | GSE197685 | GEO

Hydrogen sulfide (H2S) modulates lifespan of C.elegans

2013-07-30 | E-GEOD-16975 | biostudies-arrayexpress

RNA-seq of CN, CN/AML, and CN/AML BAALC KO iPSCs-derived HSPCs

Project description:RNA-seq of CN, CN/AML, and CN/AML BAALC KO iPSCs-derived HSPCs

| PRJEB43341 | ENA

Pseudodesulfovibrio strain:SYK

Project description:Pseudodesulfovibrio sp. SYK

| PRJDB14204 | ENA