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accession-icon GSE146109
VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.

Sample Metadata Fields

Age, Specimen part, Cell line, Treatment

View Samples
accession-icon GSE146108
VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading [HBMEC]
  • organism-icon Homo sapiens
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.

Publication Title

VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.

Sample Metadata Fields

Specimen part, Cell line, Treatment

View Samples
accession-icon GSE146107
VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading [mouse heart]
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.

Publication Title

VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.

Sample Metadata Fields

Age, Specimen part

View Samples
accession-icon GSE92680
Expression data from CD4+ T cells isolated from inguinal lymph nodes 7 days post MOG immunization
  • organism-icon Rattus norvegicus
  • sample-icon 17 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

We isolated CD4+ T cells from draining lymph nodes 7 days post EAE from

Publication Title

Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬.

Sample Metadata Fields

Sex, Specimen part

View Samples
accession-icon GSE14302
Identification of human Myc- and Lin-28B-responsive transcripts
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

In order to examine the consequences of Myc and Lin-28B induction on the transcriptome, P493-6 cells (human EBV-transformed B lymphocytes) were infected with a retrovirus that produces human Lin-28B or empty virus as a control. Gene expression profiles were then monitored in the high and low Myc state using Affymetrix microarrays.

Publication Title

Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE620
Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line
  • organism-icon Homo sapiens
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

Most individuals with cystic fibrosis (CF) carry one or two mutations that result in a maturation defect of the full-length CFTR protein. The deltaF508 mutation results in a mutant protein that is degraded by the proteasome instead of progressing to the apical membrane where it functions as a cyclic AMP-regulated chloride channel. 4 phenylbutyrate modulates heat shock protein expression and promotes trafficking of deltaF508 thus permitting maturation and membrane insertion. The goal of this study was to gain insight into the genetic mechanism of PBA action through a large-scale analysis of gene expression. The Affymetrix genome spanning U133 microarray set was used to compare mRNA expression in untreated IB3-1 cell line cultures with cultures treated with 1mM 4-phenylbuyterate for 12 and 24 hr. IB3-1 deltaF508/W1282X) bronchial epithelial cells were cultured in T75 flasks with gentamicin-free LHC-8 medium. Cells were fed with 10 ml of media every 2 to 3 days. After reaching 80% confluence cells were treated with 1 mM PBA. A T75 flask of confluent IB3-1 cells was rinsed twice with ice cold Hanks buffer then scraped into 3ml of ice cold TRIzol (Gibco BRL) then rinsed with 3 ml ice cold TRIzol and the mRNA was isolated according to the TRIzol protocol. A total of 5 control cultures, 3 cultures with 12 hr BPA application and 3 cultures with 24 hr PBA application were processed

Publication Title

Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP036130
Global transcriptional Analysis of Yap/Yki Orthologs in Drosophila melanogaster by RNA Seq
  • organism-icon Drosophila melanogaster
  • sample-icon 15 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of their myriad developmental functions. Here we analyze the molecular evolution of the proto-oncogene YAP/Yorkie, a key effector of the Hippo signaling pathway that controls organ size in both Drosophila and mammals. Based on heterologous functional analysis of evolutionarily distant Yap/Yorkie orthologs, we demonstrate that a structurally distinct interaction interface between Yap/Yorkie and its partner TEAD/Scalloped became fixed in the eumetazoan common ancestor. We then combine transcriptional profiling of tissues expressing phylogenetically diverse forms of Yap/Yorkie with ChIP-seq validation in order to identify a common downstream gene expression program underlying the control of tissue growth in Drosophila. Intriguingly, a subset of the newly-identified Yorkie target genes are also induced by Yap in mammalian tissues, thus revealing a conserved Yap-dependent gene expression signature likely to mediate organ size control throughout bilaterian animals. Combined, these experiments provide new mechanistic insights while revealing the ancient evolutionary history of Hippo signaling. We sought to define the downstream target genes of selected Yap variants by performing RNA sequencing analysis (RNA-seq) on total RNA isolated from GMR-Gal4>Yap eye discs. Overall design: Transcriptional profiles were generated in triplicate from eye imaginal disks with either endogenous Yki, or GMR-Gal4 over-expressed Yki, Trichoplax Yap, Monosiga Yap, or Monisiga Yap+TEAD domain, using deep sequencing via Illumina Hi Seq.

Publication Title

Molecular evolution of the Yap/Yorkie proto-oncogene and elucidation of its core transcriptional program.

Sample Metadata Fields

Treatment, Subject

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accession-icon GSE2395
Human Cystic Fibrosis
  • organism-icon Homo sapiens
  • sample-icon 40 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

Summary: CF patients homozygous for the DF08 DF08 genotype present a full range of phenotypic manifestations that exist within the pulmonary system. This project aims to identify candidate genes that influence the severity of pulmonary disease

Publication Title

Respiratory epithelial gene expression in patients with mild and severe cystic fibrosis lung disease.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE76347
Phase 2 Study of Digitoxin for the Treatment of Airway Inflammation in Cystic Fibrosis
  • organism-icon Homo sapiens
  • sample-icon 46 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

Cystic Fibrosis lung disease progresses by a combination of accelerated airways inflammation and bacterial colonization and infection. Airways inflammation in CF is predominantly neutrophilic and complicates airway clearance therapies through cellular debris, excessive DNA, excessive and viscous mucous, and high concentrations of neutrophils,Il-8 and related cytokines liberated along the NFkB signaling pathway. We conducted a single site, randomized, double blind, placebo-controlled, proof-of-concept trial in which we evaluated the effects of 28 days of two dose levels (0.05 mg and 0.10 mg daily) of an older cardiac glycoside, digitoxin, as compared with placebo, on inflammatory markers in induced sputum obtained from 24 subjects with mild to moderate CF lung disease. Nasal epithelial cells from 23 subjects were analyzed for microarray analysis. CF patients 18 to 45 years old, any genotype combination, were eligible.

Publication Title

Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding.

Sample Metadata Fields

Specimen part, Disease, Disease stage, Treatment, Subject, Time

View Samples
accession-icon GSE6714
RNA polymerase is poised for activation across the genome
  • organism-icon Drosophila melanogaster
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

Regulation of gene expression is integral to the development and survival of all organisms. Transcription begins with the assembly of a pre-initiation complex at the gene promoter, followed by initiation of RNA synthesis and the transition to productive elongation. In many cases, recruitment of RNA polymerase II (Pol II) to a promoter is necessary and sufficient for activation of gene. However, there are a few notable exceptions to this paradigm, including heat shock genes and several proto-oncogenes, whose expression is attenuated by regulated stalling of polymerase elongation within the promoter-proximal region. To determine the importance of polymerase stalling for transcription regulation, we performed a genome-wide search for Drosophila genes with promoter-proximally stalled Pol II. Our data reveal that stalling is widespread, occurring at hundreds of genes that respond to stimuli and developmental signals, indicating a role for regulation of polymerase elongation in the transcriptional responses to dynamic environmental and developmental cues.

Publication Title

RNA polymerase is poised for activation across the genome.

Sample Metadata Fields

No sample metadata fields

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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