EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Yasuhiro Yamada
PROVIDER: E-GEOD-72898 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation. Microarray in mouse EWS-FLI1-induced osteosarcoma cell lines(SCOS#2 and SCOS#12) and sarcoma(SCOS#2)-derived iPSCs. Total 6 samples were analyzed. We can induce EWS-FLI1 expression by Doxycycline-inducible expression system in SCOS#2 and #12. We investigaed EWS-FLI1 activated genes (Dox ON-High) and EWS-FLI1 repressed genes (Dox OFF-High) in SCOS#2 and #12 sarcoma cell lines. Also, we investigated global gene expression pattern of sarcoma-derived iPSCs (iPSC#2-A1 and #2-B5). A link to this sample file can be found below.
2016-03-01 | E-GEOD-72704 | biostudies-arrayexpress
Project description:EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation. Chip-seq in mouse EWS-FLI1-induced osteosarcoma cell lines (SCOS#2 )
2016-03-01 | E-GEOD-72897 | biostudies-arrayexpress
Project description:By using patient-derived xenografts (PDXs) as living surrogate of the clinical practice, we identify here induction of genes related to the IFN pathway as an early and specific predictor of tumor response to treatment. Gene expression profile of tumor cells after laser-capture microdissection of residual tumor foci to characterize the molecular changes occurring in residual tumor cells surviving chemotherapy RNA was extracted from microdissected areas using the RNeasy Mini kit (Qiagen, Valencia, CA). This approach allowed isolating foci of human tumor cells from the murine stroma. Gene expression analysis was performed with Affymetrix Exon 1.0 ST microarrays. Hybridization, data normalization and statistical analysis were outsourced to GenoSplice Technology (Paris, France).
2015-12-31 | E-GEOD-58990 | biostudies-arrayexpress
Project description:Cdx2/IL-1beta mice have less intestinal metaplasia at the squamocolumnar junction thanIL-1beta mice alone. This study was to identify a mechanism for this effect by examining differences in gene expression patterns when Cdx2 is co-expressed. We dissected out intestinal metaplasia nodules from the squamocolumnar junction in Cdx2/IL-1beta mice and Il-1beta mice and measured gene expression on a Mouse Gene 2.0ST Affymetrix array in Oct 2013.
2016-08-01 | E-GEOD-60320 | biostudies-arrayexpress
Project description:A toxicogenomic analysis from liver of different pharmacological active coumarins (mammea A/BA+A/BB 3:1 and soulatrolide ) was performed on mice treated (20mg/kg/daily) for a whole week to evaluate if such compounds possess or could develop a hazardous profile on liver. In this dataset, we include the expression data obtained from dissected liver mouse treated with active coumarins (obtained from Calophyllum brasiliense) and control (SSI) for a whole week. Livers from 4 animals per treatment and control were subjected to RNA extraction. These data showed 46 genes up and 72 downregulated genes for mammea coumarins and 665 up and 1077 downregulated genes . Expression data from liver of mice treated with different coumarins (mammea and soulatrolide) from Calophyllum brasiliense 12 Total samples were analyzed. Liver from 4 animals per treatment groups were subjected to mRNA expression analysis. We generated the statistical computing and metrics in the arrayQualityMetrics data were normalized with RMA method and differential expressed genes obtained with Ingenuity Software. Genes with an FDRâ¤10% and a fold-change â¥2 were selected.
2015-09-06 | E-GEOD-72755 | biostudies-arrayexpress
Project description:With aging, significant changes in circadian rhythms occur, including a shift in phase toward a âmorningâ chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmannâs areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life. Using the resources of the University of Pittsburghâs Brain Tissue Donation Program, 210 subjects were identified. Samples were obtained after consent from next-of-kin during autopsies conducted at the Allegheny County Medical Examinerâs Office (Pittsburgh, USA). The absence of lifetime psychiatric disorders was determined by an independent committee of experienced clinical research scientists using information from clinical records, toxicology results and a standardized psychological autopsy. Subjects of unwitnessed death were removed from the study. A total of 146 individuals with the following characteristics were analyzed in this study: mean (range) age of 50.7 (16-96) years, 78% male, 85% Caucasian, mean postmortem interval (PMI) for brain collection 17.3 (4.8-28) hours, mean pH 6.7 (5.8-7.6) and RNA integrity number (RIN) 8.0 (5.9-9.6). For each subject, the right hemisphere was blocked coronally, frozen and stored at -80C. Blocks containing Brodmann area 11 (BA11) or Brodmann area 47 (BA47) of the orbital PFC were cut on a cryostat, and cortical gray matter was collected for RNA extraction as previously described. All procedures were approved by the University of Pittsburghâs Institutional Review Board for Biomedical Research and Committee for Research Involving the Dead.
2015-12-31 | E-GEOD-71620 | biostudies-arrayexpress
Project description:Foxi3 is a transcription factor expressed in the hair follicle epithelium during development and postnatally. In this study we used a microarray analysis to indentify differentially expressed genes in Foxi3 null epithelium compared to Foxi3 wt epithelium. We used E15.5 stage as the earliest time point when the Foxi3 null hair phenotype bacame obvious, to find out the most early consequences of Foxi3 ablation. Dispase-dissociated back skin epithelia of 4 Foxi3 total null and 4 wild-type E15.5 mouse embryos, littermates from 4 litters of C57/Bl6 background, were used for the analysis. Array and data analysis were performed in the Biomedicum Functional Genomics Unit (University of Helsinki, Finland).
2016-03-01 | E-GEOD-68985 | biostudies-arrayexpress
Project description:Complement inhibitor C4b-binding protein (C4BP) is synthesized in liver and pancreas and composed of 7 identical alpha chains and one unique beta chain. We showed previously that C4BP binds islet amyloid polypeptide (IAPP) and affects fibril formation in vitro. Now we found that polymeric C4BP inhibited lysis of human erythrocytes incubated with monomeric IAPP while no erythrocyte lysis was observed after incubation with preformed IAPP fibrils. In contrast, monomeric alpha chain of C4BP had significantly reduced activity. Further, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in decreased cell viability, which was restored in the presence of physiological concentrations of C4BP. Accordingly, addition of C4BP rescued the ability of INS-1 cells and isolated rat islets to respond to glucose stimulation with insulin secretion, which was impaired in the presence of IAPP alone. C4BP was internalized together with IAPP into INS-1 cells and therefore we aimed to study its effect on gene expression. Pathway analyses of mRNA expression microarray data indicated that cells exposed to C4BP and IAPP in comparison to IAPP alone increased expression of genes involved in cholesterol synthesis. Depletion of cholesterol through methyl-β-cyclodextrin or cholesterol oxidase abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells. Also, inhibition of phosphoinositide 3-kinase but not NF-κB had a similar effect. Taken together, one of the mechanisms by which C4BP protects beta-cells from IAPP cytotoxicity is by enhancing cholesterol synthesis. The INS-1 cells were grown as 5 separate clones for 10 passages before plating in a 12-well plate (Nunc) at 100.000 cells per well and grown in complete RPMI 1640 medium to 70% confluency for approximately 48 h. The cells were then challenged by adding 77 μM monomeric IAPP alone or together with C4BP (0.6 μM). DMSO (1%) used as solvent for IAPP as well as C4BP (0.6 μM) alone were used as controls. RNA was extracted after 10h incubation and analysis carried out using Rat Gene 2.0 array chip (Affymetrix).
2016-08-25 | E-GEOD-79224 | biostudies-arrayexpress
Project description:The clinical application of doxorubicin as a broad-spectrum anti-tumor antibiotic is limited greatly by its cardiotoxicity. Various mechanisms have been studied, but little is known about whether genes or pathways relevant with energy metabolism contributes to doxorubicin-induced cardiomyopathy or not. We used microarrays to detail the global expression profiling of acute cardiomyopathy induced by doxorubicin in wild type or CHIP knockout C57BL/6J mice and discovered distinct classes of changed genes during this process. The whole hearts were selected for RNA extraction and hybridization on Affymetrix microarrays at day 5 after a single intraperitoneal injection of doxorubicin at a dose of 15 mg/kg.
2014-07-23 | E-GEOD-59672 | biostudies-arrayexpress
Project description:Subsequently to primary growth, most dicotyledonous plants undergo secondary growth leading to an increased diameter of growth axes. During secondary growth initiation in shoots, a cylindrical meristem, the vascular cambium, is established by the initiation of meristematic activity in interfascicular regions, a process that ultimately leads to the formation of a continuous cylinder of vascular tissue along the shoot axis. In Arabidopsis this happens in a reduced area at the very base of the stem. In this study, a transcriptional comparison between the base and the first internode has been performed in order to asses the physiological state of both sample types and search for potential key regulators of the process. Total RNA was extracted from the base and the first internode from stems of 15cm tall Arabidopsis plants (ecotype Col-0). After RNA amplification, Cy3 or Cy5 targets were produced. Three independent biological replicates were used for each type of sample. Three hybridizations were performed, representing the three independent biological replicates, being one of them a dye swap.
2010-06-05 | E-GEOD-15446 | biostudies-arrayexpress