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accession-icon GSE89325
Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/choroid in chick model of form-deprivation myopia
  • organism-icon Gallus gallus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Chicken Genome Array (chicken)

Description

Microarray analysis was performed on retina/RPE/choroid samples taken from the right eyes of male chicks across control and recovery from form deprivation conditions.

Publication Title

Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia.

Sample Metadata Fields

Sex, Specimen part, Treatment, Time

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accession-icon SRP016076
Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation
  • organism-icon Drosophila melanogaster
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression. Overall design: To study the development and differentiation of the CNS midline cells of Drosophila melanogaster on a genome-wide scale, these cells were labeled with GFP using the GAL/UAS system and FACS purified at 2 ermbryonic time-points; 6-8 hours and 14-16 hours after egg laying. Poly(A) mRNA was collected from these samples and cDNA libraries were generated. Sequencing was performed on 6 independent samples: Two FACS purified CNS-midline cell samples and one non-midline sample taken from 6-8 hours After Egg Laying (AEL) embryos and from 14-16 hours AEL embryos.

Publication Title

Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.

Sample Metadata Fields

Specimen part, Subject, Time

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accession-icon GSE33830
Gene Bionetworks Involved in Epigenetic Transgenerational Inheritance of Environmentally Altered Sexual Selection: Role of Epigenetics in Evolutionary Biology
  • organism-icon Rattus norvegicus
  • sample-icon 132 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.

Publication Title

Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE14269
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior
  • organism-icon Rattus norvegicus
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.

Publication Title

Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP105325
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against Mantle Cell Lymphoma cells
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1, and the NFkB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the level of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared to ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Co-treatment of ARV-771 with ibrutinib or the BCL2-antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior pre-clinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or resistant MCL. Overall design: Twelve samples in biologic triplicates

Publication Title

BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.

Sample Metadata Fields

Subject

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accession-icon GSE26737
Epigenetic Transgenerational Alterations to Stress Response in Brain Gene Networks and Behaviour
  • organism-icon Rattus norvegicus
  • sample-icon 48 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individuals life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring the phenotype into being.

Publication Title

Epigenetic transgenerational inheritance of altered stress responses.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP055392
Genetic disruption of COX-1 inhibits multiple oncogenic pathways
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500

Description

We performed RNA sequencing in isogenic models of COX-1 proficient (OV3/SCR) and COX-1 deficient (OV3/COX1KD) OVCAR-3 ovarian cancer cells. COX-1 knockdown was associated with a coordinated anti-oncogenic phenotype, with growth, angiogenesis, migration/invasion, and epithelial-mesenchymal transition among the pathways down-regulated. Overall design: RNA sequencing was performed at Vanderbilt Technologies for Advanced Genomics (VANTAGE) using Illumina HiSeq 2500.

Publication Title

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP028528
Homo sapiens Transcriptome or Gene expression
  • organism-icon Homo sapiens
  • sample-icon 25 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Transcriptome sequencing of Chronic Phase and Blast Crisis CML, normal cord blood cells, and normal cord blood cells transduced with lentiviral vectors

Publication Title

ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE14365
Expression data from WT and Aire deficient mTECs
  • organism-icon Mus musculus
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED.

Publication Title

Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE66708
NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells
  • organism-icon Homo sapiens
  • sample-icon 744 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene Expression Array (primeview), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.

Sample Metadata Fields

Disease, Cell line, Treatment

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

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