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GSE35038
Mus musculus
29 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anti-cancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling towards senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development.
Publication Title
DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global analysis of brassinosteroid (BR)-mediated gene expression under abiotic stress identifies BR associated mechanisms of stress tolerance, and new stress-related genes
Publication Title
Gene expression and functional analyses in brassinosteroid-mediated stress tolerance.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 46 Downloadable Samples
Illumina HiSeq 2500
Description
Tumor hypoxia is associated with poor patient outcome and resistance to therapy. It is associated with a rapid decline in protein production mediated through mTOR signalling. Here we show that it also leads to widespread changes in splicing and a global shift towards the expression of noncoding isoforms, thus providing a novel and orthogonal mechanism by which cells can modulate protein expression. Overall design: Examination of mRNA levels in HCT116 cells after 0 hr, 1 hr, 2 hr and 24 hr in hypoxia. Three biological replicates each.
Publication Title
Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Using our computational method SynGeNet to evaluate genomic and transcriptomic data characterizing four major genomic subtypes of melanoma, we selected the top ranked drug combination for BRAF-mutation melanoma for subsequent validaiton. Here we present drug-induced gene expression data from the BRAF-mutant A375 melanoma cell line in response to four treatment conditions: vehicle control (DMSO), vemurafenib alone, tretinoin (ATRA) alone and vemurafenib+tretinoin combination. Overall design: Gene expression profiles of A375 melanoma cells were generated by RNAseq (Illumina HiSeq 4000) under the following treatment conditions: vehicle control (DMSO), vemurafenib, tretinoin and vemurafenib + tretinoin combination.
Publication Title
Synergy from gene expression and network mining (SynGeNet) method predicts synergistic drug combinations for diverse melanoma genomic subtypes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Previously it has been shown that Id3 can act as an apoptosis-inducer gene in immortalized human keratinocytes. To further investigate the role of Id3 in the progression of skin cancer, the role of Id3 in A431 cells is investigated through ectopic induction of Id3.
Publication Title
Id3 induces an Elk-1-caspase-8-dependent apoptotic pathway in squamous carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we analyzed the effect of REST knock-out on the ability to these cells to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective down-regulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals.
Publication Title
A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Given the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown screen of PI modulator genes in human AML cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its knockdown results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent upon activation of the mTOR pathway. Critically, however, PIP4K2A knockdown in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency which we suggest may be the consequence of the regulation of different transcriptional programmes in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy.
Publication Title
A targeted knockdown screen of genes coding for phosphoinositide modulators identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and survival.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
As macrophages are the primary site of Mtb infection and are sites of vitamin D signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D).
Publication Title
Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: To identify the impact of thermoneutral housing as opposed to standard housing on gene expression profiles in the mouse peripheral blood mononuclear cells (PBMCs), focusing on proinflammatory immune responses and high-fat diet induced non-alcoholic fatty liver disease pathogenesis. Methods: Expression profiles from PBMCs collected from C57Bl6 mice fed chow or high-fat diet for 8 weeks, following 2 weeks at either standard or thermoneutral housing conditions. Sequencing was performed in duplicate, the Illumina HiSeq 2500. Transcripts that passed quality filters were analyzed at the gene level, using Strand NGS for accurate alignment and quantification. Results: We mapped approximately 20million reads per sample to the mm10 genome using annotations produced by Ensembl, which represented 36186 transcripts. Approximately 14000 genes exhibited reasonable expression in at least one experimental condition. The primary focus was the effect of housing temperature while holding diet consistent (i.e. thermoneutral vs standard, both on high-rat diet), where ~2700 genes exhibited differential regulation. Conclusions: We present the transcriptomic profile of PBMCs from mice fed chow of high-fat diets, following either standard or thermoneutral housing. We obseve an augmented proinflammatory immune response. Overall design: PBMC expression profiles were characterized following eight weeks of chow or high-fat diet, following two weeks of standard or thermoneutral housing.
Publication Title
Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects.
Publication Title
The anti-fibrotic effect of mycophenolic acid-induced neutral endopeptidase.
Sample Metadata Fields
No sample metadata fields
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