IPH-926 is an anticancer drug-resistant tumor cell line derived from a chemo-refractory human infiltrating lobular breast cancer (ILBC). IPH-926 ILBC cells were subjected to gene expression profiling using an Affymetrix HG U133 Plus 2.0 array.
ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells.
Specimen part, Cell line
View SamplesHuman solid tumors contain rare cancer side population (SP) cells, which expel the fluorescencent dye H33342 and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays this study investigated differential gene expression between SP and non-SP (NSP) cells isolated from the CAL-51 human mammary carcinoma cell line.
Down-regulation of the fetal stem cell factor SOX17 by H33342: a mechanism responsible for differential gene expression in breast cancer side population cells.
Specimen part
View SamplesMolecular profiling of cerebral gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification and IDH1/2 mutation status.
Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups.
Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sex, Age
View SamplesThe pathogenesis of diffuse large B cell lymphomas (DLBCL) is only partly understood. We analyzed 148 DLBCL by high resolution single nucleotide polymorphism (SNP)-chips to characterize genomic imbalances. Seventy-nine cases were of the germinal center B-cell like (GCB) type of DLBCL, 49 of the activated B-cell like (ABC) subtype and 20 were type 3 DLBCL. Twenty-four regions of recurrent genomic gains and 38 regions of recurrent genomic losses were identified over the whole cohort, with a median of 25 imbalances per case for ABC-DLBCL and 19 per case for GCB-DLBCL. Several recurrent copy number changes showed differential frequencies in the GCB- and ABC-DLBCL subgroups, including gains of HDAC7A predominantly in GCB-DLBCL (38% of cases) and losses of BACH2 and CASP8AP2 predominantly in ABC-DLBCL (35%), hinting at disparate pathogenetic mechanisms in these entities. Correlating gene expression and copy number revealed a strong gene dosage effect in all tumors, with 34% of probesets showing a concordant expression change in affected regions. Two new potential tumor suppressor genes emerging from the analysis, CASP3 and IL5RA, were sequenced in 10 and 16 candidate cases, respectively. However, no mutations were found, pointing to a potential haploinsufficiency effect of these genes, considering their reduced expression in cases with deletions. This work thus describes differences and similarities in the landscape of genomic aberrations in the DLBCL subgroups in a large collection of cases, confirming already known targets, but also discovering novel copy number changes with possible pathogenetic relevance.
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sex, Age
View SamplesHair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis.
Reprogramming adult dermis to a neonatal state through epidermal activation of β-catenin.
No sample metadata fields
View SamplesBefore and after anaerobic Fe(II) shocked WT and ?bqsR of late stationary phase P. aeruginosa PA14 strains Associated publication: Kreamer NN, Costa F, Newman DK. 2015. The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance. mBio 6(1):e02549-14. doi:10.1128/mBio.02549-14. Overall design: Expression profiles of rRNA-depleted total RNA from WT and ?bqsR Fe(II)-shocked (before and after 30 min incubation with 200 µM ferrous ammonium sulfate ) cultures grown anaerobically to deep stationary phase (A500 = 0.8) in Fe-limited (1 µM ferrous ammonium sulfate) MOPS minimal medium containing succinate as the carbon source, in triplicate
The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance.
Cell line, Subject
View SamplesIn deceased donor kidney transplantation, acute kidney injury (AKI) prioir to surgery is a major determinant of delayed graft function (DGF), but AKI is histologically silent and difficult to assess. We hypothesized that a molecular measurement of AKI would add power to conventional risk assessments to predict the early poor allograft function at first week post transplantation.
Comparing molecular assessment of implantation biopsies with histologic and demographic risk assessment.
Specimen part
View SamplesEffects of aneuploidy on gene expression in Arabidopsis thaliana containing extra copies of chromosome 5.
Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.
Specimen part, Subject
View SamplesHigh uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level, remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knock down of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium. Overall design: Puromycin-selected HUVEC (Human Umbilical Vein Endothelial Cells, Lonza, Switzerland) cells, expressing either scrambled control (SCR) or anti-EZH2 short-hairpin (shEZH2) constructs (at total 7 days after the first viral transduction), were used in FSS experiments (72h of control static culture or exposure to 20 dynes/cm2 of fluid shear stress, using Ibidi pump system (in µ-Slides I 0.4 Luer, Ibidi, Planegg/Martinsried, Germany)). Each replicate experiment consisted of viral transductions and puromycin selection of a separate HUVEC batch, followed by the FSS experiment. Two FSS experimental sets of the same HUVEC batch were run every time in parallel and lysed at the same end time point, one in RNAse-free conditions with RNA-Easy Mini Plus kit RLT Plus lysis buffer (QIAGEN, Venlo, The Netherlands), and one with RIPA buffer. The RIPA-lysates were analyzed with Western blotting and confirmed the complete (no protein present) knock-down of EZH2. From the RNA-lysates, RNA was isolated using the RNA-Easy Mini Plus kit (QIAGEN, Venlo, The Netherlands). High quality RNA samples (pre-assessed by Nanodrop measurements) were further processed in the Genome Analysis Facility of the University Medical Center Groningen. The RNA quality and integrity were verified using PerkinElmer Labchip GX with a cut-off value of 9 (scale 1 to 10, where 9 is very high quality RNA). RNA library was created in accordance with the TruSeqTM RNA Sample Preparation v2 Guide (Illumina, San Diego, CA, USA), using the PerkinElmer Sciclone liquid handler, resulting in 330bp cDNA fragments. The paired-end sequencing (100bp reads) was performed using the Illumina HiSeqTM 2500. (Quoted from the Materials and Methods of the related manuscript, with adjustments).
The decrease in histone methyltransferase EZH2 in response to fluid shear stress alters endothelial gene expression and promotes quiescence.
No sample metadata fields
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