Differential expression and pathway enrichment in neutrophils treated with Ruxolitinib and vehicle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA794200 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17434157.fastq.gz | Fastqsanger.gz | |||
| SRR17434158.fastq.gz | Fastqsanger.gz | |||
| SRR17434159.fastq.gz | Fastqsanger.gz | |||
| SRR17434160.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:We report the effect of rexolitinib on neutrophil function, by extracting mouse bone marrow neutrophils, and after treatment with Ruxolitinib and vehicle, extracting neutrophil RNA from each group for RNA-seq. Finally, we show that Ruxolitinib produces functional effects on neutrophils mainly through inflammatory signaling pathways, amplifying the immune effects of neutrophils in an inflammatory environment and accelerating neutrophil death.
2022-01-04 | GSE193055 | GEO
Project description:Day 0= whole skin from C57/B6 female at 8.5 weeks of age Day5= whole skin from C57/B6 female after 4 days of treatment with vehicle, ruxolitinib or tofacitinib
2018-05-27 | GSE69300 | GEO
Project description:Transplant recipients of IDH2-R140Q JAK2-V617F expressing bone marrow were treated with AG221 and ruxolitinib monotherapy, combined therapy, or vehicle. LSKs were sorted from terminal samples and sequenced with three WT controls.
2018-02-22 | GSE95771 | GEO
Project description:Unleashing anti-tumor T cell activity by checkpoint inhibition is effective in many cancer patients but clinical response rates remain limited. Myeloid derived suppressor cells erode antitumor lymphocyte numbers and function, and correlate with resistance to checkpoint inhibitors. By screening small molecule libraries, we identified JAK inhibitors’ ability to rescue T cell function. Despite its documented immune suppressive properties, the prototypical JAK inhibitor ruxolitinib enhanced the efficacy of immune checkpoint blockade in cancer. This effect correlated with loss of suppressive gene expression, and acquisition of immunostimulatory molecular markers and T cell stimulatory activity in myeloid cells. In preclinical models, ruxolitinib significantly improved the function and increased the total numbers of activated tumor-infiltrating NK and CD4 T cells compared to checkpoint blockade alone and the efficacy was conditional on granulocytic cells. In addition to myeloid reprogramming in the tumor, ruxolitinib blunts G-CSF signaling in the bone marrow to prevent expression of suppressive and chemotaxis genes in neutrophils.
2024-06-20 | GSE209647 | GEO
Project description:Background and methods: Ruxolitinib (RUX), a Jak1/2 inhibitor, has been reported to attenuate murine bone marrow failure recently. Its potential toxocicty of anemia and thrombocytopenia in human remains a concern. We tested the toxicity of ruxolitinib on hematopoiesis in normal mice by feeding the mice with RUX chow for 3 months. Bone marrow Lin-CD117+ cells were sorted from treated or untreated mice. RNA-Seq and analysis was performed using SMART-Seq mRNA LP Kit (Takara) and the Illumina Novaseq6000, according to the Institute's protocols. Results: Ruxolitinib reduced RBC and lymphocytes, but did not affect NEU and PLT in normal mice. RNA sequencing demonstrated that HSPCs from RUX-treated and untreated mice had overlapped transcriptome distribution in multiple dimentional scalling plot, indicating overall similarity at molecular level. Conclusion: Our results demonstrate that ruxolitinib has minimal toxicity on hematopoiesis in normal mice.
2024-05-08 | GSE240866 | GEO
Project description:Aplastic anaemia (AA) is a disease that shows complex pathogenesis involving multiple immune factors. While immunosuppressive therapies such as cyclosporine can effectively control AA, they may be ineffective in certain patients or those with relapse. Therefore, new treatments are needed. Among the targets for these treatments, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway regulates inflammatory cytokines and immune activation. Ruxolitinib, a JAK1/2 inhibitor, reduces T-cell activation and the associated inflammatory response and improves AA disease status in mice. However, its mechanism of action is unclear; thus, further research is needed before its clinical use. We previously showed increased pyroptosis in patients with severe AA (SAA) and that macrophage pyroptosis is an important factor in immune activation. The current study investigated the interaction of ruxolitinib with macrophages and whether the drug could treat SAA by improving pyroptosis levels. We induced differentiation of the THP-1 human monocyte cell line into macrophages in vitro and then induced pyroptosis. After constructing a macrophage pyroptosis model, treatment with different concentrations of ruxolitinib was administered. The results showed that ruxolitinib reduced the levels of pyroptosis and inflammatory-related factors. A mouse model of SAA was validated. In conclusion, ruxolitinib may treatment affects SAA by reducing the level of macrophage pyroptosis.
2025-03-18 | GSE291850 | GEO
Project description:To investigate the effects of IL-1β/IL-6/PGE2 on neutrophil modulation, we performed RNA-seq to compare IL-1β/IL-6/PGE2-treated neutrophils to vehicle-treated neutrophils.
2022-12-12 | E-MTAB-12367 | biostudies-arrayexpress
Project description:Methods: Methods: To better understand the role of resveratrol in the regulation of neutrophils activation and function, neutrophils with or without resveratrol in the expose of LPS were compared in a transcriptome sequencing study. Total RNA was isolated from bone marrow and FACS-separated neutrophils. Transcriptome sequencing libraries were generated using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and sequenced on an Illumina Hiseq platform (Illumina, San Diego, CA). Sequences were aligned to the reference genome with TopHat and processed with Cufflinks, which quantifies each transcript in each sample using reference annotations produced bythe University of California Santa Cruz UCSC. Differentially expressed genes with a fold change of >=2.0 and p value<0.01 between resveratrol treated and control neutrophils were submitted to GO and KEGG enrichment analysis, which uses unbiased methods to assess pathway enrichment. Results: Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that downregulated genes from resveratrol-stimulated neutrophils are involved in neutrophil migration, neutrophil chemotaxis, TNF signaling pathway and cytokine activity, among other. Compared to control neutrophils, neutrophils with resveratrol exhibited downregulated levels of cell survival related genes (Camkk1, Aqp1, Bcl2a1b, etc), cell cycle related genes (Ccnb1, Ccnb2, Cdc20, Cdk1, etc), adhesion and migration related genes (Cass4, Nectin4, Gp5, Gpr35, etc), and cytokines (Csf1, Csf3, Ccl2, Ccl7, Ccl12).
2023-02-09 | GSE215236 | GEO
Project description:Ruxolinitib was approved by the FDA for the treatment of JAK2-V617F positive myelofibrosis. Unexpectedly, treatment of JAK2-V617F expressing cells with ruxolitinib causes paradoxical hyperphosphorylation of JAK2 at Tyr1007/1008 sites. The mechanism of ruxolitinib-induced JAK2 hyperphosphorylation is not well understood. A ruxolitinib-resistant JAK2 variant (V617F+L983F) and a JAK2-V617F kinase dead mutant (JAK2-V617F+K882R) did not show paradox hyperphosphorylation after ruxolitinib treatment indicating that ruxolitinib-mediated JAK2 hyperphosphorylation is mediated by a JAK2 intrinsic mechanism. Native immunocomplexes of JAK2-V617F with an antibody against pTyr1007/1008 could be blocked by the presence of ruxolitinib, although JAK2-V617F was hyperphosphorylated at these sites, suggesting that in the presence of ruxolitinib the JAK2 activation loop is buried within the kinase domain. This stabilization of the activation loop conformation results in the protection of pTyr1007/1008 sites from phosphatases. When JAK2 is in an inhibited conformationally restricted state, the phosphate group of Tyr1007 and Tyr1008 forms an intermolecular interaction with Arg975 and Lys999, respectively. Mutation of Arg975 and Lys999 to Ala reduced the phosphorylation at both Tyr1007/1008 residues, and importantly, ruxolitinib treatment did not lead to JAK2 hyperphosphorylation in these variants. Hyperphosphorylated JAK2 is hyperactive after ruxolitinib dissociation and activates STAT5 target genes PIM2, ID1, and MPL. Our results suggest a novel mode of kinase regulation by modulating kinase activity through conformational changes induced by ruxolitinib.
2025-02-01 | GSE284481 | GEO
Project description:Purpose: Investigate the neutrophils could exspress different mRNA de novo from PGE2 stimulation. Methods: Isolated bone marrow neutrophils with Percoll gradient are treated with 10 μM of PGE2 for 24 hours. Results: Qualified sequence reads per sample to the mouse genome (mm10) with Bowtie2 or STAR were processed with StringTie and identified genes. Conclusion : 1,359 genes were significantly different in PGE2 treated bone marrow neutrophils from vehicle treated ones.
2022-08-01 | GSE199773 | GEO