Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237275 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]
| PRJNA237276 | ENA
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: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
Project description:Mutations in the endoplasmic reticulum (ER) chaperone calreticulin (CALR) are common in myeloproliferative neoplasm (MPN) patients, activate the thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling. The mechanisms by which CALR mutations cause myeloid transformation are incompletely defined. We employed mass spectrometry proteomics to identify novel CALR-mutant interacting proteins. Mutant CALR caused mislocalization of binding partners and increased recruitment of FLI1, ERP57 and CALR to the MPL promoter to enhance transcription. CALR 52 mutant was also found to increase genome-wide recruitment of Fli1 to the chromatin. Overall, these results show that type 1 CALR mutant modulates Fli1 cellular localization and recruitment.
2018-09-19 | GSE120134 | GEO
Project description:The mechanisms that mediate transformation in MPN are not fully delineated and clinically utilized JAK inhibitors have limited ability to reduce disease burden or reverse myelofibrosis. Here we show that MPN progenitor cells are characterized by marked alterations in gene regulation through differential enhancer utilization, and identify Nfb signaling as a key pathway activated in malignant and non-malignant cells in MPN. Genetic and functional studies underscore the central role of JAK/STAT signaling in myeloproliferative neoplasms (MPNs). However, the mechanisms that mediate transformation in MPNs are not fully delineated, and clinically utilized JAK inhibitors have limited ability to reduce disease burden or reverse myelofibrosis. Here we show that MPN progenitor cells are characterized by marked alterations in gene regulation through differential enhancer utilization, and identify nuclear factor kB (NF-kB) signaling as a key pathway activated in malignant and non-malignant cells in MPN. Inhibition of BET bromodomain proteins attenuated NF-kB signaling and reduced cytokine production in vivo. Most importantly, combined JAK/BET inhibition resulted in a marked reduction in the serum levels of inflammatory cytokines, reduced disease burden, and reversed bone marrow fibrosis in vivo.
2017-12-14 | GSE91062 | GEO
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: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.
2014-06-03 | GSE54645 | GEO
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.
2014-06-03 | GSE54644 | GEO