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SRP112886
Homo sapiens
12 Downloadable Samples
NextSeq 500
Description
We have investigated the effects of CDK8/19 inhibitor Senexin B on NF?B-mediated transcription, induced by a canonical NF?B activator, TNFa. Overall design: HCT116 cells were pre-treated with or without 1 µM Senexin B for 1 hour, followed by 2 hour treatment with 10 ng/ml TNFa. Each treatment condition was done in biological triplicate.
Publication Title
CDK8/19 Mediator kinases potentiate induction of transcription by NFκB.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Identfification of MEF2A target genes using ChIP-exo and RNA-seq in skeletal muscle and primary cardiomyocytes. MEF2 plays a profound role in the regulation of transcription in cardiac and skeletal muscle lineages. To define the overlapping and unique MEF2A genomic targets, we utilized ChIP-exo analysis of cardiomyocytes and skeletal myoblasts. Of the 2783 and 1648 MEF2A binding peaks in skeletal myoblasts and cardiomyocytes, respectively, 294 common binding sites were identified. Genomic targets were compared to differentially expressed genes in RNA-seq analysis of MEF2A depleted myogenic cells. Overall design: The effect of MEF2A gene silencing on gene expression in myoblasts was assessed at 48 hr DM. Up and downregulated genes were then compared to MEF2A target genes identified in ChIP-exo analysis of 48 hr DM C2C12 myoblasts cells and primary cardiomyocytes.
Publication Title
Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Profile of RNA expression in a C-33A cell line derived from an HPV negative cervical carcinoma in the presence or absence of HPV1 E2 expression. Overall design: mRNA profiles of C-33A cells in presence or absence of HPV1 E2 expression were generated by deep sequencing using Illumina GAIIx. Two samples (no replicates). One control and one experimental.
Publication Title
The effect of Rho kinase inhibition on long-term keratinocyte proliferation is rapid and conditional.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
Publication Title
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Sample Metadata Fields
Cell line, Treatment
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We use genetic manipulations of regulators representing different pathways to examine whether transcriptomes progressively resemble dietary restriction when multiple regulators are perturbed.
Publication Title
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 13 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Background: The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also expressed in animals with more complex body plans. To this end, we have applied Micro-Array Profiling of Caenorhabditis elegans Cells (MAPCeL) to muscle cell populations extracted from developing Caenorhabditis elegans embryos. Results: Fluorescence Activated Cell Sorting (FACS) was used to isolate myo-3::GFP-positive muscle cells, and their cultured derivatives, from dissociated early Caenorhabditis elegans embryos. Microarray analysis identified 6,693 expressed genes, 1,305 of which are enriched in the myo-3::GFP positive cell population relative to the average embryonic cell. The muscle-enriched gene set was validated by comparisons to known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type-specific expression profiling and reveal that 60% of these transcripts have human homologs.
Publication Title
The embryonic muscle transcriptome of Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Background:
Publication Title
The embryonic muscle transcriptome of Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 3 Downloadable Samples
Description
Dietary restriction (DR) is the most powerful natural means to extend lifespan. Here we obtain temporally resolved transcriptomes during calorie restriction and intermittent fasting in Caenorhabditis elegans, and find that early and late responses involve metabolism and cell cycle/DNA damage, respectively.
Publication Title
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 3 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients.
Publication Title
Induction of stable drug resistance in human breast cancer cells using a combinatorial zinc finger transcription factor library.
Sample Metadata Fields
No sample metadata fields
View Samples