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GSE51020
Homo sapiens
10 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MYC-amplified medulloblastomas are highly lethal tumors. BET bromodomain inhibition was recently described to downregulate MYC-associated transcriptional activity in various cancer subtypes. To investigate whether JQ1, a BET bromodomain inhibitor is downregulation MYC and MYC-associated transcriptional activity, we performed global gene expression profiling of five medulloblastomas MYC-amplified patient-derived cell lines treated by JQ1 and the inactive form of JQ1.
Publication Title
BET bromodomain inhibition of MYC-amplified medulloblastoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
NextSeq 500
Description
Breast cancer cell lines containing stable dox inducible shRNAs targeting SF3B1 were profiled by RNA sequencing. We determined the effect of gene expression and splicing changes before and after knocking down SF3B1 in cell lines with normal copy number (SF3B1neutral) or partial copy loss (SF3B1loss) cell lines Overall design: RNA profiles for SF3B1 suppression were generated from 8 breast cancer cell line pairs (-/+ dox) with no techincal replicates.
Publication Title
Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells (strain L) and cultured.
Publication Title
Genetic and transcriptional evolution alters cancer cell line drug response.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type by oncogenic insults or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in DFCI-1 medium retain a fraction with progenitor cell properties. These cells co-express basal, luminal and stem/progenitor cell markers. Clonal derivatives of progenitors co-expressing these markers fall into two distinct types: K5+/K19- (Type I) and K5+/K19+ (Type II). We show that both types of progenitor cells have self-renewal and differentiation ability. Through microarray analysis, we want to identify genes and pathways linked to human mammary epithelial stem/progenitor cell self-renewal and differentiation.
Publication Title
Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global programme of gene expression after knockdown of Ecdysoneless in hMECs
Publication Title
The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6NKp46 DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear.
Publication Title
IL-15 sustains IL-7R-independent ILC2 and ILC3 development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ada3 (alteration/deficiency in activation) is a transcriptional adaptor that forms a core structural component of multiple HAT complexes. In order to gain insights into physiological roles of Ada3, we made a conditional knockout mouse for Ada3 which was early embryonic lethal. Deletion of Ada3 in MEFs by using Adenovirus-Cre showed changes in global histone acetylation.
Publication Title
Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals is proclaimed to have value-added clinical potential in the regeneration of complex cell types like cardiomyocytes. Despite the availability of several small molecule inhibitors capable of modulating specific receptor-ligand interaction or enzymatic activity, no bioactive synthetic DNA-binding inhibitor targeting key cell fate-controlling gene like SOX2 is available yet. Herein, we demonstrate a novel DNA-based chemical approach to guide hiPSCs differentiation using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing the knowledge about key transcriptional changes associated with cardiomyocyte induction, we developed a PIP termed SOX-L targeting 5-CTTTGTT-3 sequence and demonstrate the inhibition of SOX2-DNA interaction and mesoderm induction of hiPSCs. Genome-wide gene analyses revealed that SOX-L remarkably specified cardiac mesoderm by triggering targeted alteration in SOX2-associated gene regulatory networks. Also, employment of SOX-L along with a Wnt inhibitor successfully generated spontaneously contracting cardiomyocytes to validate our concept that DNA-binding inhibitors like PIPs could be used for directed differentiation of hiPSCs. Because PIPs could be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to directly target and distinctively regulate key transcription factor associated with the desired cell type.
Publication Title
A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Acute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
Publication Title
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Pyrrole-imidazole polyamides (PIPs) have been shown to inhibit gene expression by interrupting the DNA-protein interface. Human Ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor which plays a key role in many aggressive forms of cancer. We have developed a novel pyrroleimidazole polyamide, PIP1 targeting the REL/ELK1 binding site in the EVI1 minimal promoter that can significantly repress the expression of EVI1 in MDA-MB-231 cells. Whole-transcriptome analysis revealed that a fraction of EVI1-driven genes were modulated by PIP1.
Publication Title
Targeted suppression of EVI1 oncogene expression by sequence-specific pyrrole-imidazole polyamide.
Sample Metadata Fields
Specimen part, Cell line
View Samples