This SuperSeries is composed of the SubSeries listed below.
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Specimen part, Cell line, Treatment
View SamplesHeat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state.
Specimen part, Cell line, Treatment
View SamplesA unifying characteristic of aggressive cancers is a profound anabolic shift in metabolism to enable sustained proliferation and biomass expansion. The ribosome is centrally situated to sense metabolic states but whether it impacts systems that promote cellular survival is unknown. Here, through integrated chemical-genetic analyses, we find that a dominant transcriptional effect of blocking protein translation in cancer cells is complete inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for tumorigenesis. Translational flux through the ribosome reshapes the transcriptional landscape and links the fundamental anabolic processes of protein production and energy metabolism with HSF1 activity. Targeting this link deprives cancer cells of their energy and chaperone armamentarium thereby rendering the malignant phenotype unsustainable.
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state.
Specimen part
View SamplesMM.1S orthotopic tumors were analyzed fro their gene expression upon tumor outgrowth. In contorl/bortezomib/elesclmol and combo treatments. Overall design: examination of three tumors for each condition.
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Cell line, Subject
View SamplesWe transiently induce the Lo19S state with a dox inducible shRNa targeting PSMD2 and explore the gene expression in the presence and absence of bortezomib Overall design: one cell type (T47D), two states (Control and Lo19S) with and without treatment with 20nM bortezomib , all in triplicates
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Cell line, Subject
View SamplesT lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.
Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.
Specimen part, Cell line, Subject
View SamplesThe purpose of this experiment was to identify genes responding differently to a 24 h low red to far red ratio (R:FR) treatment in plants grown at 16 and 22 degrees
Light-quality regulation of freezing tolerance in Arabidopsis thaliana.
Age
View SamplesMotivation: RNA-seq is replacing microarrays as the primary tool for gene expression studies. Many RNA-seq studies have used insufficient biological replicates, resulting in low statistical power and inefficient use of sequencing resources. Results: We show the explicit trade-off between more biological replicates and deeper sequencing in increasing power to detect differentially expressed (DE) genes. In the human cell line MCF-7, adding more sequencing depth after 10M reads gives diminishing returns on power to detect DE genes, while adding biological replicates improves power significantly regardless of sequencing depth. We also propose a cost-effectiveness metric for guiding the design of large scale RNA-seq DE studies. Our analysis showed that sequencing less reads and perform more biological replication is an effective strategy to increase power and accuracy in large scale differential expression RNA-seq studies, and provided new insights into efficient experiment design of RNA-seq studies Overall design: Treatment (10nM E2 treatment for 24h) and control MCF7 cells are both replicated 7 times, and collected for mRNA-seq. Reads are then subsampled for statistical analysis.
RNA-seq differential expression studies: more sequence or more replication?
No sample metadata fields
View SamplesEwg differentially regulated genes in 16-18 h Drosophila embryos. The experiment contains expression measurements from wild type, ewg l1 protein null allele and ewg l1 elavEWG (elavEWG rescue construct expressing a ewg cDNA from the elav promoter) mutants.
Erect wing regulates synaptic growth in Drosophila by integration of multiple signaling pathways.
Age
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