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GSE85570
Homo sapiens
437 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate -H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual -H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed 2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of -H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
Publication Title
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To gain insight in the kinetics and interplay of the predominant transcriptional responses of DNA damage signalling pathways in undifferentiated cells, mouse embryonic stem cells were exposed to cisplatin at four different time points (2, 4, 8 and 24 hr) and concentrations (1, 2, 5 and 10 uM). RNA was isolated and subjected to genome-wide expression profiling.
Publication Title
A portrait of cisplatin-induced transcriptional changes in mouse embryonic stem cells reveals a dominant p53-like response.
Sample Metadata Fields
Specimen part, Compound, Time
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ficolled AML-M0 sample gene expression profiles on Affymetrix HGU133Plus2.0 GeneChips. Acute myeloid leukemia (AML) classified as FAB-M0 is defined as a subtype with minimally differentiated morphology. Here we investigated by gene expression (GEP) profiling whether AML-M0 cases should be considered as one or more unique molecular subgroups that discriminates them from other AML patients. By applying GEP and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate that AML-M0 cases express a unique signature. Hematological transcription regulators such as CEBPA, CEBPD, PU.1 and ETV6 and the differentiation associated gene MPO appeared strongly down-regulated, in line with the very primitive state of this type of leukemia. Moreover, AML M0 cases appeared to have a strong positive correlation with a previously defined immature AML subgroup with adverse prognosis. AML-M0 leukemias frequently carry loss-of-function RUNX-1 mutation and unsupervised analyses revealed a striking distinction between cases with and without mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B-cell-related genes, e.g. members of the B-cell receptor complex, transcriptions regulators RUNX3, ETS2, IRF8 or PRDM1 and major histocompatibility complex class II genes. Importantly, expression of one single gene, i.e. BLNK, enabled prediction of RUNX1 mutations in AML-M0 with high accuracy. We propose that RUNX1 mutations in this subgroup of AML cause lineage infidelity, leading to aberrant co-expression of myeloid and B-lymphoid genes in the same cells.
Publication Title
Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
We used RNA-seq and Ribo-seq analyses to examine the effect of CPT treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) using biological duplicates of control and CPT-treated (5 hrs) MCF7 cells
Publication Title
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
Description
We used RNA-seq and Ribo-seq analyses to examine translation efficiency (TE) in PC9 and H1933 cells Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in PC9 and H1933 cell lines
Publication Title
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
Description
We used RNA-seq and Ribo-seq analyses to examine the effect of Nutlin3a (activator of p53) treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in control and Nutlin3a-treated (20 hrs) MCF7 cells
Publication Title
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
We applied deep-sequencing based technique, 3''-Seq, to obtain comprehansive maps of poly-A sites in human cells. 3''-Seq was applied to two cell lines (U2OS and RPE-1), in control and PABPN1 knockdown cells Overall design: Examination of poly-A sites in control and PABPN1kd cells (in two different cell lines)
Publication Title
The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Epithelial (CD31-CD45-EpCAM+) cells were isolated by FACS from Grhl2-deficient (Shh-Cre;Grhl2f/-) and control (Shh-Cre;Grhl2f/+) embryonic lungs at day E16.5 (3 biological replicates/genotype). Total RNA extracted from the samples was subjected to next-generation sequencing (NGS) library preparation using standard Illumina protocols. Completed libraries from individual samples were sequenced on a HiSeq2500 at the Australian Genome Research Facility. Overall design: RNA-seq was performed on Grhl2-deficient and control epithelium isolated from the lungs of E16.5 embryos (n=3 replicates/genotype/cell population).
Publication Title
Lung morphogenesis is orchestrated through Grainyhead-like 2 (Grhl2) transcriptional programs.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Background. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene.Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL.Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.
Publication Title
Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We previously established long-term 3D organoid culture systems for several murine tissues (intestine, stomach, pancreas and liver) as well as human intestine and pancreas. Here, we describe culture conditions to generate long-term 3D culture from human gastric stem cells. The technology can be applied to study the epithelial response to infection with Helicobacter pylori. Human gastric cultures can expand indefinitely in 3D Matrigel. Cultures can be generated from normal tissue, from single sorted stem cells, or from tumor tissue. Organoids maintain many characteristics of the respective tissue in terms of histology, marker expression and euploidy. Organoids from normal tissue express markers of four lineages of the stomach and self-organize in gland and pit-domains. They can be directed to specifically express either lineages of the gastric gland, or the gastric pit by addition of Nicotinamide and withdrawal of Wnt. While gastric pit lineages react marginally to bacterial infection, gastric gland lineages mount a strong inflammatory response. The gastric culture system provides a unique tool to study gastric pathologies.
Publication Title
In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples