NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE193053 | GEO | 2024/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:We use a novel microfluidic device to provide different concentrations of a point source of TNF-α to a population of NIH3T3 mouse embryonic fibroblasts. These cells are then retrieved in a spatially resolved manner (notated as near, mid, and far from point source) and sequenced using a modified version of the Smart-Seq2 protocol. We find that spatially resolved transcriptomes reveal distinct gene regulation patterns based on TNF dose and/or distance from the point source
2022-09-20 | GSE189062 | GEO
Project description:Constitutively active RAS plays a central role in the development of skin cancer in the classical two stage skin carcinogenesis in mice and in a number of human cancers. Ras-mediated tumor formation is commonly associated with upregulation of cytokines and chemokines that mediate an inflammatory response considered relevant to oncogenesis. MyD88 is a crucial intermediate in the expression of multiple innate immune responders through signaling from the Toll-like/IL-1R family. We report that mice ablated for MyD88 or the IL-1R are resistant to topical skin carcinogenesis, and cultured MyD88-/- keratinocytes transduced with an oncogenic ras vector form only a few small tumors in orthotopic grafts. Initiated keratinocytes arising from oncogenic activation of ras are hyperproliferative but also resist signals for induced differentiation and upregulate a host of pro-inflammatory genes. Ras-transduced MyD88-/- keratinocytes are also hyperproliferative but the differentiation response is intact and pro-inflammatory genes are not upregulated. Using both genetic and pharmacological approaches, we find that in keratinocytes, the differentiation and immune regulation functions mediated by oncogenic ras require the establishment of an autocrine loop through IL-1α and its receptor leading to NF-κB activation. In the absence of MyD88 or IL-1R, this loop cannot be established. Further, blocking the IL-1a mediated NF-κB activation in ras-transduced wildtype keratinocytes corrects the defect in both differentiation response and proinflammatory gene expression. Collectively, these results demonstrate that ras activation converts normal keratinocytes to an initiated phenotype through a series of potentially reversible feedback signals that provide therapeutic opportunities through inhibition of IL-1 signaling. Gene expression comparison of wild type ras-transformed keratinocytes untreated (n=3) or treated (n=3) in vitro with the IL1R antagonist Anakinra.
2011-08-28 | E-GEOD-22777 | biostudies-arrayexpress
Project description:NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli
| PRJNA794193 | ENA
Project description:Constitutively active RAS plays a central role in the development of skin cancer in the classical two stage skin carcinogenesis in mice and in a number of human cancers. Ras-mediated tumor formation is commonly associated with upregulation of cytokines and chemokines that mediate an inflammatory response considered relevant to oncogenesis. MyD88 is a crucial intermediate in the expression of multiple innate immune responders through signaling from the Toll-like/IL-1R family. We report that mice ablated for MyD88 or the IL-1R are resistant to topical skin carcinogenesis, and cultured MyD88-/- keratinocytes transduced with an oncogenic ras vector form only a few small tumors in orthotopic grafts. Initiated keratinocytes arising from oncogenic activation of ras are hyperproliferative but also resist signals for induced differentiation and upregulate a host of pro-inflammatory genes. Ras-transduced MyD88-/- keratinocytes are also hyperproliferative but the differentiation response is intact and pro-inflammatory genes are not upregulated. Using both genetic and pharmacological approaches, we find that in keratinocytes, the differentiation and immune regulation functions mediated by oncogenic ras require the establishment of an autocrine loop through IL-1α and its receptor leading to NF-κB activation. In the absence of MyD88 or IL-1R, this loop cannot be established. Further, blocking the IL-1a mediated NF-κB activation in ras-transduced wildtype keratinocytes corrects the defect in both differentiation response and proinflammatory gene expression. Collectively, these results demonstrate that ras activation converts normal keratinocytes to an initiated phenotype through a series of potentially reversible feedback signals that provide therapeutic opportunities through inhibition of IL-1 signaling.
2011-08-29 | GSE22777 | GEO
Project description:Microfluidic devices provide a low-input and efficient platform for single-cell RNA-seq (scRNA-Seq). Here we present microfluidic diffusion-based RNA-seq (MID-RNA-seq) for conducting scRNA-seq with a diffusion-based reagent swapping scheme. This device incorporates cell trapping, lysis, reverse transcription and PCR amplification all in one microfluidic chamber. MID-RNA-Seq provides high data quality that is comparable to existing scRNA-seq methods while implementing a simple device design that permits multiplexing. The robustness and scalability of MID-RNA-Seq device will be important for transcriptomic studies of scarce cell samples.
2019-02-25 | GSE119271 | GEO
Project description:Investigation in bacterial transcriptomics is widely used to investigate gene regulation, bacterial susceptibility to antibiotics, host-pathogen interactions, and pathogenesis. Transcriptomics is crucially dependent on suitable methods to isolate and detect bacterial RNA. Microfluidic approaches offer ways of creating integrated point-of-care systems, analysing a sample from preparation, RNA isolation through to detection. Critical for on-chip diagnostics to deliver on their promise is that mRNA expression is not altered through the use microfluidic sample processing. Here, we investigate the impact on the use of a microfluidic sample processing system based on hydrodynamic separation upon RNA expression of bacteria isolated from blood to prove its suitability for further microfluidic test development. A 10 array study using total RNA recovered from bacteria isolated using the microfluidic device and total RNA recovered from bacteria that were not separated using the device were compared. Arrays were performed in 5 biological replicates from each condition
2016-04-01 | E-GEOD-68064 | biostudies-arrayexpress
Project description:Sample preparation is a crucial step in bottom-up proteomics. Analytical performances of bottom-up proteomics can be improved by the miniaturization of sample preparation steps. Many microfluidic devices are proposed in the field of proteomics. But many of them are not capable of handling complex sample and do not integrate the processing and digestion steps. We propose a ChipFilter Proteolysis (CFP) microfluidic device derived from the Filter Aided Sample Preparation FASP method for the miniaturization of protein processing and digestion steps in bottom-up proteomics. The microchip has two reaction chambers of 0.6 µL volume separated by a protein filtration membrane in regenerated cellulose. Cell lysis, protein concentration and rapid chemical and enzymatic treatment can be performed in our microfluidic device. Complex proteomic samples like yeast protein extract have already been analyzed with our microchip. Compared to the traditional FASP method, our microfluidic device offers a better proteome coverage with ten times less starting material and eight times quicker protocol.
2020-04-29 | PXD016742 | Pride
Project description:Sample preparation is a crucial step in bottom-up proteomics. Analytical performances of bottom-up proteomics can be improved by the miniaturization of sample preparation steps. Many microfluidic devices are proposed in the field of proteomics. But many of them are not capable of handling complex sample and do not integrate the processing and digestion steps. We propose a ChipFilter Proteolysis (CFP) microfluidic device derived from the Filter Aided Sample Preparation FASP method for the miniaturization of protein processing and digestion steps in bottom-up proteomics. The microchip has two reaction chambers of 0.6 µL volume separated by a protein filtration membrane in regenerated cellulose. Cell lysis, protein concentration and rapid chemical and enzymatic treatment can be performed in our microfluidic device. Complex proteomic samples like yeast protein extract have already been analyzed with our microchip. Compared to the traditional FASP method, our microfluidic device offers a better proteome coverage with ten times less starting material and eight times quicker protocol.
2020-04-29 | PXD018066 | Pride
Project description:In this study, we used a doxycycline (DOX) inducible gene expression system to introduce MyD88, a gene associated with lymphoma, into the U2932 lymphoma cell line. We performed a transcriptomic analysis (RNA-seq) to identify differentially expressed genes due to the MyD88 L265P oncogenic mutation. This study aimed to investigate the impact of MyD88 L265P oncogenic signaling on lymphoma cells by analyzing the transcriptomic response of model cell lines.
2023-06-06 | GSE226797 | GEO