Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237274 | ENA |
REPOSITORIES: ENA
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Project description:Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]
| PRJNA237276 | ENA
Project description:Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [HEL cell lines]
| PRJNA237275 | ENA
Project description:Activation of the JAK/STAT pathway in Behcet’s Disease
| PRJNA261006 | ENA
Project description:Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) and JNK-dependent manner. Genetic depletion of macrophages, or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-M-NM-:B signalling made no contribution to the phenotype observed. These results identify an evolutionarily conserved M-bM-^@M-^Xscavenger receptor-JNK-Type 1 cytokineM-bM-^@M-^Y cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) and JNK-dependent manner. Genetic depletion of macrophages, or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-M-NM-:B signalling made no contribution to the phenotype observed. These results identify an evolutionarily conserved M-bM-^@M-^Xscavenger receptor-JNK-Type 1 cytokineM-bM-^@M-^Y cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway 5 biological samples were FACS-sorted from different batches of Drosophila melanogaster males after 30 days on 15% lipid enriched diet (n=5) and control diet (n=5)
2015-01-30 | E-GEOD-63254 | biostudies-arrayexpress
Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [HEL cell lines] We have performed gene expression profiling in the JAK2V617F homozygous mutant HEL cell line following treatment with 2 independent shRNAs targeting JAK2 or 2 different control shRNAs
2014-06-03 | E-GEOD-54645 | biostudies-arrayexpress
Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [MPN patients] We have performed microarray gene expression analysis in 93 patients with MPNs (28 PV, 47 ET, 18 MF) and 11 age-matched normal donors.
2014-06-03 | E-GEOD-54644 | biostudies-arrayexpress
Project description:Emerging evidence indicates that various cancers, including prostate, breast, melanoma and lung cancers, could gain resistance to targeted therapies by acquiring lineage plasticity. Although various genomic and transcriptomic aberrations correlate with lineage plasticity-driven resistance, the molecular mechanisms and kinetics of acquiring lineage plasticity are not fully elucidated. Through integrated transcriptomic and single cell RNA-seq (scRNA-seq) analysis of more than 80,000 cells, we show that the ectopic activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway drives lineage plasticity and Androgen Receptor (AR) targeted therapy resistance in PCa with TP53/RB1-deficiency. Ectopic activation of JAK-STAT signaling enables Heterogeneous and AR-independent subclones to emerge upon the selective pressure of AR targeted therapy, including subclones expressing multi-lineage, progenitor-like and epithelial to mesenchymal transition (EMT)-like lineage survival transcriptional programs. Both genetic and pharmaceutical inactivation of key components of the JAK-STAT signaling pathway significantly re-sensitizes resistant PCa tumors to AR targeted therapy. In summary, these results show for the first time that JAK-STAT signaling pathway is a key effector in driving lineage plasticity and represents a potential therapeutic target for overcoming AR targeted therapy resistance.
2022-06-29 | GSE175975 | GEO
Project description:NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expressions of drug-metabolizing genes in liver. However, the role of NFIC1 in breast cancer is not clear. Here we showed that increased expression of NFIC1 suppressed the migration and invasion of MCF-7 cells. The activation of interferon-associated Jak-STAT pathway was enhanced with NFIC1 overexpression. NFIC1 overexpression upregulated the expression of IFNB1, IFNL1, IFNL2 and IFNL3. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion. In addition, we found that MX1 and MX2 were the target genes of NFIC1- activated Jak-STAT pathway, which mediated the migration and invasion of MCF-7 cells. These results demonstrated that NFIC1 inhibited the migration and invasion in MCF-7 cells through interferon mediated activation of Jak-STAT pathway, indicating that Jak-STAT pathway might be a potential therapeutic target for preventing breast cancer metastasis.
2023-03-01 | GSE197755 | GEO
Project description:The consitutive activation of the JAK/STAT signalling cascade is reponsible for the majority of meyoproliferative disorders in humans, a disease that is also conserved in Drosophila. A gain-of-function mutation in the Drosophila JAK kinase leads to blood cell (haemocyte) overproliferation which eventually is manifested as black melanotic tumors. Haemocyte-like Drosophila Kc167 cells were used to identify downstream target genes of the JAK/STAT pathway which may be responsible for tumour generation and progression. Experiment Overall Design: Kc167 cells were activated with the principal JAK/STAT pathway ligand Unpaired (UPD) in a time course manner. To this end, for each transcript profiling condition and time point, biological duplicates were activated with UPD or Mock conditioned media for 30 min, and total RNA was extracted 2, 4 or 10h after initial addition of conditioned media. 12 samples were used for hybridization to the arrays.
2009-09-12 | E-GEOD-15584 | biostudies-arrayexpress
Project description:JAK/STAT pathway plays important roles in controlling Drosophila intestinal homeostasis and regulating the ISC proliferation and differentiation. However,the downstream targets of its transcription factor-STAT92E remain largely unknown.To further identify the regualtory mechanisms of the JAK/STAT pathway in controlling intestinal homeostasis,we performed the ChIP-Seq assay with mouse raised STAT92E antibody using JAK/STAT signaling highly activated adult intestines.Through the ChIP assay, we have identified over 1000 significant peaks (p<0.01) around the putative targets.The well-characterized JAK/STAT downstream targets including Domeless,Socs36E,STAT92E and chinmo were identified in our ChIP assay,indicating that our experiment is workable to identify novel JAK/STAT downstream targets in adult intestines.This work will provide insights into our understanding of regulatory mechanisms of JAK/STAT signaling during Drosophila intestinal development. Identify the ChIP peaks of STAT92E antibody using JAK/STAT signaling highly actived Drosophila adult intestines, compared with input libaray as the control
2015-05-12 | E-GEOD-67346 | biostudies-arrayexpress