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SRP179641
Homo sapiens
8 Downloadable Samples
NextSeq 500
Description
Approximately 30% of women diagnosed with ERa breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD) undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse in vivo while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of tumors from prospectively recruited patients shows that KRT80 levels correlate with stiffer tumors in vivo. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment. Overall design: Total RNA profiling of MCF7 breast adenocarcinoma cell line and MCF7 overexpressing KRT80. Experiments were carried out in four replicates in both cell lines.
Publication Title
SREBP1 drives Keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins. Cell line UPMM3 contains a frameshift mutation in BAP1. Overall design: RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins
Publication Title
GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Sex, Age, Cell line, Treatment
View Samples- Oryza sativa
- 24 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
In response to bacterial infection, early transcriptional re-programming occurs in the host plant.
Publication Title
Antagonistic, overlapping and distinct responses to biotic stress in rice (Oryza sativa) and interactions with abiotic stress.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Transcriptomes of mouse embryonic autopods were generated detecting expression of approximately 26179 transcripts in the developing forelimb or hindlimb autopods, representing about 58 % of the probe sets on MOE-430 A/B GeneChip. Three biological replicate array experiments were finished for each condition and MAS5.0 signal were used to do data analysis. Forty-four transcripts with expression differences higher than 2-fold were detected(T test, P<0.05), including Tbx4, Tbx5, Hoxc10 and Pitx1 which were previously shown to be differentially expressed in developing forelimb and hindlimb bud by in situ hybridization and SAGE study (Margulies 2001). RTPCR and in situ experiments confirmed several top differentially expressed genes which were newly discovered by our experiments. Vast amount of transcripts and its family members such as Bmp, Fgf, Epha, Wnt, T-box and Hox families detected to be highly expressed or differentially expressed in developing autopods, suggesting that the complexity of transcriptomes of developing autopods and dynamic differential expression and differential combinations of gene expression signals in the developing limb tissue contributes to differences in forelimb versus hindlimb patterning. The differentially expressed genes are the essential factors for morphological diversification of developing limb structures.
Publication Title
Transcriptome analysis of the murine forelimb and hindlimb autopod.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Here, we present a systematic and quantitative test of the hypothesis that the composition and activities of the endoplasmic reticulum (ER) proteostasis network impact mutational tolerance of secretory pathway client proteins. We focus on influenza hemagluttinin (HA), a viral coat protein that folds in the host's ER via a complex but well-characterized pathway. By integrating chemical methods to modulate the unfolded protein response with deep mutational scanning to assess mutational tolerance, we discover that upregulation of ER chaperones broadly enhances HA mutational tolerance across numerous sites and secondary/tertiary structure elements, including sites targeted by host antibodies. Remarkably, this host chaperone-enhanced mutational tolerance is observed at the same HA sites where mutational tolerance is most reduced by propagation at a fever-like temperature. Thus, host ER proteostasis mechanisms and temperature modulate HA mutational tolerance in opposite directions. This finding has important implications for influenza evolution, because influenza immune escape is contingent on HA possessing sufficient mutational tolerance to acquire antibody resistance while still maintaining the capacity to fold and function. More broadly, this work provides the first experimental evidence that the composition and activities of the ER proteostasis network critically define the mutational tolerance and, therefore, the evolution of secretory pathway client proteins. Overall design: RNA-seq characterizing a clonal HEK293T-Rex cell line, expressing DHFR ATF6f, Tet XBP1s, and the tetracycline repressor. These cell lines were treated with small molecules for 24 hours (in triplicate) to modulate the proteostasis environment in a stress-independent manner, at either 37C or 39C. XBP1s was activated by treatment with 0.1 ug/mL Doxycycline; ATF6f/XBP1s were activated by treatment with 0.1 ug/mL Doxycycline and 1 uM TMP; basal cells were vehicle-treated (0.01% DMSO). These cells were previously characterized in Shoulders et al. Cell Reports, 2013.
Publication Title
Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the “A12-resin,” that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids including human sera. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293T cells cultured in medium depleted of Zn(II) using S100A12. Our data indicate that dividing cells can maintain a constant pool of free Zn(II), even under conditions of severe Zn(II) deprivation. We expect that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis in biological settings, uncovering novel roles for Zn(II) in biology. Overall design: Defining the response of a cell line to Zn(II) starvation
Publication Title
A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and Evaluation of Cellular Consequences of Zn(II) Deficiency.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions.
Publication Title
Endurance exercise as a countermeasure for aging.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Sample Metadata Fields
Specimen part, Treatment
View Samples