Gene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS)
Cediranib for metastatic alveolar soft part sarcoma.
Time
View SamplesAuxin-dependent transcript abundance was assayed by transferring 6 day old Arabidopsis grown on a a nylon mesh to IAA-containing or control media
A kinetic analysis of the auxin transcriptome reveals cell wall remodeling proteins that modulate lateral root development in Arabidopsis.
Specimen part
View SamplesWe were interested in characterizing the transcriptional changes that occur on a genome-wide scale following treatment of EGFR-mutant lung cancer cells with targeted therapies.
Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways.
Specimen part, Cell line, Treatment
View SamplesThe goals of this study is to test whether NICD presence protects the RBPjk-null Hair Follicles by altering gene expression via association with other DNA binding proteins at P3, just before the conversion to TSLP-producing keratin cysts. Overall design: Methods: Skin samples were embedded in OCT. Sectioned at 20µm thickness. Dehydrated in EtOH, and equilibrated to Xylene before the LCM procedure. Laser capture was performed with Arcturus Veritas. Methods: ~100 hair follicles from Notch-null, PS-null, RBPjk-null and wild-type samples were pooled into 3 biological replicates for each genotype and subjected to RNA isolation followed by RNA-Seq. Conclusions: A total of 2047 genes were differentially expressed (=1.5 fold) in three or more biological replicates of Notch mutant hair follicles compared to wild-type controls (p-value<0.05). Unsupervised hierarchical clustering analysis failed to distinguish between the mutants.
The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development.
Cell line, Subject
View SamplesDrosophila mosaic eye-antennal discs from the listed genotypes generated using the MARCM system were dissected from 3rd instar larvae at day 5 after egg deposition.
The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in Drosophila melanogaster through maintaining a progenitor-like cell state.
Specimen part
View SamplesThe transcription factor STAT3 is constitutively activated in tumors of different origin but the molecular bases for STAT3 addiction of tumor cells have not yet been clearly identified. We generated knock/in mice carrying the constitutively active Stat3 allele, Stat3C, and showed that Stat3C could enhance Neu oncogenic power, triggering the production of earlier onset, more invasive mammary tumors. Tumor-derived cell lines displayed higher migration and invasion and disrupted distribution of cell-cell junction markers. The tensin family member Cten (C-Terminal Tensin-like), known to mediate EGF-induced migration and highly expressed in inflammatory breast cancer, was up-regulated in both Neu;Stat3C cells and tumors. Both Cten expression and enhanced migration were strictly dependent on Stat3, and Cten silencing normalized cell migration and rescued cell-cell contact defects. Importantly, the pro-inflammatory cytokine IL-6 could mediate Cten induction in MCF10 cells, in an exquisitely Stat3-dependent way. This model allowed us to shed some light on the oncogenic role of Stat3 in the breast, suggesting moreover a mechanism through which inflammatory signals can cooperate with EGF receptors in inflammatory breast cancer.
Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten.
No sample metadata fields
View SamplesThe recently proposed exozyme hypothesis posits that subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic test of this hypothesis, we examine the role of Dis3 -- an essential polypeptide with endo- and 3'' to 5'' exo-ribonuclease activity -- in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutation: (i) accumulate anaphase and pre-anaphase mitotic spindles; (ii) exhibit spindles that are mis-oriented and displaced from the bud neck; (iii) harbor elongated spindle-associated astral MTs; (iv) have an increased G1 astral MT length and number; and (v) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4 -- but not other exosome subunit gene mutants -- also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and microtubule-related transcripts in mutant strains. Collectively, the different mitotic phenotypes and distinct sets of mRNAs affected by the exosome subunit and cofactor mutants studied here suggest that Dis3 has a core exosome-independent role(s) in cell cycle progression. These observations are consistent with the predictions of the exozyme hypothesis and also suggest an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs, and mitotic progression. Overall design: RNA-seq analysis of total RNA harvested from WT, mtr3-1, mtr4-1, and Dis3^mtr (rrp44-1/mtr17-1) Saccharomyces cerevisiae strains after a temperature shift.
Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant.
Cell line, Treatment, Subject
View SamplesGenetic and epigenetic processes result in gene expression changes through alteration of the chromatin structure. The relative position of genes on chromosomes has therefore important functional implications and can be exploited to model microarray datasets. Gliomas are the most frequent primary brain tumours in adults and their prognosis is related to histology and grade. In oligodendrogliomas, allelic loss of 1p/19q and hypermethylation of MGMT promoter is associated with longer survival and chemosensitivity. In this work we used oligonucleotide microarray to study a group of 30 gliomas with various oligodendroglial and astrocytic components. We used an original approach combining a wavelet model of inter-probe genomic distance (CHROMOWAVE) and unsupervised method of analysis (Singular Value Decomposition) in order to discover new prognostic chromosomal patterns of gene expression. We identified a major pattern of variation that strongly correlated with survival (p= 0.007) and could be visualized as a genome-wide chromosomal pattern including widespread gene expression changes on 1p, 19q, 4, 18, 13 and 9q and multiple smaller clusters scattered along chromosomes. Gene expression changes on chromosomes 1p, 19q and 9q were significantly correlated with the allelic loss of these regions as measured by FISH. Differential expression of genes implicated in drug resistance was also a feature of this chromosomal pattern and in particular low expression of MGMT was correlated with favourable prognosis (p<0.0001). Remarkably, unsupervised analysis of the expression of individual genes and not of their chromosomal ensemble produced a pattern that could not be associated with prognosis, emphasizing the determinant role of the wavelet mathematical modelling.
Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.
No sample metadata fields
View SamplesRegulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation. Overall design: RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
No sample metadata fields
View SamplesMost hepatocellular carcinomas in younger patients from Peru arise from non-cirrhotic livers. Histological examination of the non-tumor liver tissues highlights the presence of clear cell foci in a significant fraction of Peruvian patients with hepatocellular carcinoma.
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America.
Specimen part, Disease stage, Subject
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