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accession-icon GSE136048
Placental Accreta Spectrum: Upregulated Cytotrophoblast DOCK4 Contributes to Over Invasion
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of pre-term delivery, hemorrhage and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along the scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The mRNA encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly differentially expressed molecule in PAS samples. Over-expression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up regulate a cancer-like pro-invasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.

Publication Title

Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum.

Sample Metadata Fields

Specimen part, Disease

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accession-icon SRP185844
Next Generation Sequencing of isolated EGFR+ and HLA-G+ first trimester human trophoblasts
  • organism-icon Homo sapiens
  • sample-icon 26 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

The aim of this study was to identify differentially expressed signatures of non-invasive (EGFR+) and invasive (HLA-G+) human trophoblast subtypes. These populations were isolated from single first trimester placentas from 10-12 weeks of gestation. Overall design: We performed RNAseq to analyze the global expression profile of two different trophoblastic subtypes.

Publication Title

Metabolism of cholesterol and progesterone is differentially regulated in primary trophoblastic subtypes and might be disturbed in recurrent miscarriages.

Sample Metadata Fields

Specimen part, Subject

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accession-icon SRP186159
Effect of DKK1 on embryo elongation
  • organism-icon Bos taurus
  • sample-icon 20 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 3000

Description

We report the effect of DKK1 treatment during culture on the length and transcriptome of embryos on day 15 of development, supporting the notion that changes early in development affect later stages of development. Overall design: Bovine embryos were produced in vitro and exposed to either 0 or 100 ng/ml DKK1 from day 5 to 7 of culture. Embryos were transferred on day 7 and recovered on day 15 for evaluation of length and transciptome

Publication Title

Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation.

Sample Metadata Fields

Treatment, Subject

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accession-icon GSE57674
siPools: highly complex but accurately defined siRNA pools eliminate Off-target effects
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.

Sample Metadata Fields

Cell line

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accession-icon GSE57667
siPools: highly complex but accurately defined siRNA pools eliminate Off-target effects (HuGene-1_0 ENST)
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Short interfering RNAs (siRNA) are widely used as tool for gene inactivation in basic research and therapeutic applications. One of the major shortcomings of siRNA experiments are sequence-specific Off-target effects. Such effects are largely unpredictable because siRNAs can affect partially complementary sequences and function like microRNAs (miRNAs), which inhibit gene expression on mRNA stability or translational levels.

Publication Title

siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.

Sample Metadata Fields

Cell line

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accession-icon GSE21266
Effect of Ursodeoxycholic acid on gene expression in the intestial epithelium
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Background & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy.

Publication Title

UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE19310
Expression data from wild type C. elegans and 5 osmotic stress resistant mutants exposed to hyper/isotonic environments
  • organism-icon Caenorhabditis elegans
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix C. elegans Genome Array (celegans)

Description

Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants.

Publication Title

Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.

Sample Metadata Fields

Specimen part

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accession-icon GSE9471
Diurnally regulated gene expression in the prefrontal cortex of C57Bl/6J mice at Zeitgeber Time (ZT) 3, 9, 15, and 21.
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by the sleep-wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances. Results: We examined gene expression in the mouse prefrontal cortex at four time points during the 24-hour (12-hour light:12-hour dark) cycle by microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and SCN, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed in 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by the Gene Ontology classification and by the analysis of enriched transcription factor binding sites. Conclusions: Our analysis demonstrates that ~10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioural mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythms.

Publication Title

Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE11200
Expression data from malting barley seeds
  • organism-icon Hordeum vulgare
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Barley Genome Array (barley1)

Description

Malting is seed germination under strictly controlled environmental conditions. Malting quality is a complex phenotype that combines a large number of interrelated components, each of which shows complex inheritance. Currently, only a few genes involved in determining malting quality have been characterized. This study combined transcript profiling with phenotypic correlations to identify candidate genes for malting quality.

Publication Title

Differentially expressed genes during malting and correlation with malting quality phenotypes in barley (Hordeum vulgare L.).

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE83129
RNA profiling in metastatic colorectal cancer patients treated first-line with oxaliplatin
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p

Publication Title

miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.

Sample Metadata Fields

Subject

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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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