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accession-icon GSE21364
mRNA expression data from keratinocytes with disorganized lipid raft structures (by cholesterol depletion by methyl-beta-cyclodextrin)
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Lipid rafts are cholesterol-rich cell signaling platforms and their physiological role can be explored by cholesterol depletion. To dress a global picture of transcriptional changes ongoing after lipid raft disruption, we performed whole-genome expression profiling in epidermal keratinocytes, a cell type which synthesizes its cholesterol in situ.

Publication Title

Transcriptional profiling after lipid raft disruption in keratinocytes identifies critical mediators of atopic dermatitis pathways.

Sample Metadata Fields

Specimen part, Time

View Samples
accession-icon GSE13347
FoxO RNAi in C2C12 cells
  • organism-icon Mus musculus
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

C2C12 cells are mouse skeletal muscle cells. These cells were transfected with shRNA against FoxO1, FoxO3, and FoxO4. FoxO1, FoxO3, and FoxO4 are the known paralogues expressed in this cell line.

Publication Title

Codependent activators direct myoblast-specific MyoD transcription.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP170457
Mushroom body-specific RNA sequencing to examine the role of Bap60, a core SWI/SNF subunit, in the regulation of neuronal genes.
  • organism-icon Drosophila melanogaster
  • sample-icon 15 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

RNA sequencing was used to identify genome wide transcriptional changes occurring in the Drosophila mushroom body in juvenile and mature adult flies expressing a mushroom body-specific RNAi knockdown of Bap60. The results of this analysis suggested a role for Bap60 in the regulation of neurodevelopmental genes during a critical time window of juvenile adult brain development. Overall design: RNA from mushroom body nuclei was sequenced from Drosophila melanogaster expressing a mushroom body-specific RNAi knockdown of Bap60 or mCherry (control) in both juvenile (2 and 3 replicates, respectively) and mature (5 replicates each) adult flies.

Publication Title

A Syndromic Neurodevelopmental Disorder Caused by Mutations in SMARCD1, a Core SWI/SNF Subunit Needed for Context-Dependent Neuronal Gene Regulation in Flies.

Sample Metadata Fields

Sex, Disease, Subject

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accession-icon GSE24765
Gene expression profiles of Lkb1 WT and KO hematopoietic stem cells (HSCs)
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

LKB1 encodes a Ser/Thr kinase and acts as an evolutionarily conserved sensor of cellular energy status in eukaryotic cells. LKB1 functions as the major upstream kinase to phosphorylate AMPK and 12 other AMPK-related kinases, which is required for their activation in many cellular contexts. Once activated, AMPK and AMPK-related kinases phosphorylate a diverse array of downstream effectors to switch on ATP-generating catabolic processes and switch off ATP-consuming anabolic processes, thus restoring energy balance during periods of energetic stress. To study the role and mechanisms of Lkb1 in the regulation of hematopoietic stem cell (HSC) biology, we performed transcriptome analysis of sorted LSK (Lin-, Sca-1+, c-Kit+) cells from Lkb1 WT and KO bone marrows at 1 day post-completing tamoxifen injection (DPI). To identify more proximal molecular effects, we chose 1 DPI due to the modest phenotypes in Lkb1 KO mice, yet documentation of efficient Lkb1 deletion in LSK cells at this very early time point.

Publication Title

Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE44599
ZNF365 promotes stability of fragile sites and telomeres
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Critically short telomeres activate cellular senescence or apoptosis, as mediated by the tumor suppressor p53, but in the absence of this checkpoint response, telomere dysfunction engenders chromosomal aberrations and cancer. Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability. Germline polymorphisms in the ZNF365 locus are associated with increased cancer risk, including those associated with telomere dysfunction. On the mechanistic level, ZNF365 suppresses expression of a subset of common fragile sites (CFS) including telomeres. In the absence of ZNF365, defective telomeres engage in aberrant recombination of telomere ends, leading to increased telomere sister chromatid exchange (T-SCE) and formation of anaphase DNA bridges, including ultra-fine DNA bridges (UFB), and ultimately increased cytokinesis failure and aneuploidy. Thus, the p53-ZNF365 axis contributes to genomic stability in the setting of telomere dysfunction.

Publication Title

ZNF365 promotes stability of fragile sites and telomeres.

Sample Metadata Fields

Disease, Cell line, Treatment, Time

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accession-icon GSE52667
The FoxO signature in protein breakdown
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Under stress conditions mammalian cells activate compensatory mechanisms to survive and maintain cellular function. During catabolic conditions, such as low nutrients, systemic inflammation, cancer or infections, protein breakdown is enhanced and aminoacids are released from muscles to sustain liver gluconeogenesis and tissues protein synthesis. Proteolysis in muscle is orchestrated by a set of genes named atrophy-related genes. A system that is activated both in short and prolonged stress conditions is the family of Forkhead Box (Fox) O transcription factors. Here, we report that muscle-specific deletion of FoxO members resulted in protection from muscle loss because FoxO family is required for induction of autophagy-lysosome and ubiquitin-proteasome systems. Importantly, FoxOs are required for Akt activity but not for mTOR signalling underlining the concept that FoxOs are upstream mTOR for the control of protein breakdown when nutrients are lacking. Moreover, FoxO family controls the induction of critical genes belonging to several fundamental stress response pathways such as unfolded protein response, ROS detoxification and translational regulation. Finally, we identify a set of novel FoxO-dependent ubiquitin ligases including the recent discovered MUSA11 and a new one, which we named Specific of Muscle Atrophy and Regulated by Transcription (SMART). Our findings identify the critical role of FoxO in regulating a variety of genes belonging to pathways important for stress-response under catabolic conditions.

Publication Title

Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy.

Sample Metadata Fields

Sex

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accession-icon GSE15396
Peripheral blood mononuclear, DU145, and HCT116 cells treated with a CDK inhibitor
  • organism-icon Homo sapiens
  • sample-icon 147 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE15395
HCT116 tumor cells treated with a CDK inhibitor
  • organism-icon Homo sapiens
  • sample-icon 70 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.

Publication Title

Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

Sample Metadata Fields

Cell line

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accession-icon GSE15392
DU145 tumor cells treated with a CDK inhibitor
  • organism-icon Homo sapiens
  • sample-icon 44 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.

Publication Title

Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

Sample Metadata Fields

Cell line

View Samples
accession-icon GSE15389
Peripheral blood mononuclear cells treated with a CDK inhibitor
  • organism-icon Homo sapiens
  • sample-icon 33 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.

Publication Title

Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

Sample Metadata Fields

Specimen part

View Samples
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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