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accession-icon GSE42902
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.

Publication Title

FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE17460
Expression data from MCF-7 cells transfected with miR-26a and treated or not with estradiol
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

Altered expression of microRNAs (miRNAs), an abundant class of small non-protein-coding RNAs that mostly function as negative regulators of protein-coding gene expression, is common in cancer. Here we analyze the regulation of miRNA expression in response to estrogen, a steroid hormone that is involved in the development and progression of breast carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set out to thoroughly describe miRNA expression, by using miRNA microarrays and real time RTPCR experiments, in various breast tumor cell lines in which estrogen signaling has been induced by 17-estradiol (E2). We show that the expression of a broad set of miRNAs decreases following E2 treatment in an ER-dependent manner. We further show that enforced expression of several of the repressed miRNAs reduces E2-dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent cellular response. In addition, a transcriptome analysis revealed that the E2-repressed miR-26a and miR-181a regulate many genes associated with cell growth and proliferation, including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly, miRNA expression is also regulated in breast cancers of women who had received antiestrogen neoadjuvant therapy thereby showing an estrogen-dependent in vivo regulation of miRNA expression. Overall, our data indicates that the extensive alterations in miRNA regulation upon estrogen signalling pathway plays a key role in estrogen-dependent functions and highlights the utility of considering miRNA expression in the understanding of antiestrogen resistance of breast cancer.

Publication Title

Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth.

Sample Metadata Fields

Cell line

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accession-icon SRP096911
Neuron-specific transcriptome response to loss of shep
  • organism-icon Drosophila melanogaster
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

We report RNA-seq data obtained from FACS-isolated live neurons at third instar larval or P14 pupal stage, and from BG3 cells. RNA from neurons with RNAi-based loss of shep or GFP control is used to construct stranded RNA-seq library. RNA from BG3 cells treated with dsRNA targeting shep or GFP is used to construct RNA-seq library. Overall design: RNA-seq data of loss-of-shep neurons and control neurons in larval and pupal stages, and from shep-depleted or control BG3 cells.

Publication Title

Shep regulates <i>Drosophila</i> neuronal remodeling by controlling transcription of its chromatin targets.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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accession-icon SRP007216
Messenger RNA is a functional component of a chromatin insulator complex
  • organism-icon Drosophila melanogaster
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II, Illumina HiSeq 2000

Description

Chromatin insulators are DNA-protein complexes situated throughout the genome capable of demarcating independent transcriptional domains. Previous studies point to an important role for RNA in gypsy chromatin insulator function in Drosophila; however, the identity of these putative insulator-associated RNAs is not currently known. Here we utilize RNA-immunoprecipitation and high throughput sequencing (RIP-seq) to isolate RNAs stably associated with gypsy insulator complexes. Strikingly, these RNAs correspond to specific sense-strand, spliced, and polyadenylated mRNAs, including two insulator protein transcripts. In order to assess the functional significance of these associated mRNAs independent of their coding function, we expressed untranslatable versions of these transcripts in developing flies and observed both alteration of insulator complex nuclear localization as well as improvement of enhancer-blocking activity. Together these data suggest a novel, noncoding mechanism by which certain mRNAs contribute to chromatin insulator function. Overall design: RIP-seq of insulator proteins with different library preparations and multiple biological replicates

Publication Title

Messenger RNA is a functional component of a chromatin insulator complex.

Sample Metadata Fields

Subject

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accession-icon GSE21348
Reprogramming of fibroblasts from Fragile-X patients to induced pluripotent stem cells (iPS) with defined factors
  • organism-icon Homo sapiens
  • sample-icon 13 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Human iPS cells derived from normal and Fragile-X fibroblasts in order to assess the capability of Fragile-X iPS cells to be used as a model for different aspects of Fragile-X syndrome. Microarry analysis used to compare global gene expression between human ES cells, the normal and the mutant iPS cells and the original fibroblasts, to demonstrate that the overall reprogramming process succeeded, and that the FX-iPS cells are fully reprogrammed cells.

Publication Title

Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells.

Sample Metadata Fields

Specimen part, Disease, Cell line

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accession-icon GSE42839
Expression changes in MEL cells upon differentiation and Ldb1 knockdown
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Carbonic anhydrase 1 (Car1), an early specific marker of the erythroid differentiation, has been used to distinguish fetal and adult erythroid cells since its production closely follows the - to -globin transition, but the molecular mechanism underlying transcriptional regulation of Car1 is unclear. Here, we show that Car1 mRNA decreases significantly when erythroid differentiation is induced in MEL cells. The Ldb1 protein complex including GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced enrichment of the complex during differentiation correlates with loss of Car1 expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for recruitment of Pol II as well as the transcription regulator P-TEFb to enhance elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a regulatory complex to maintain Car1 expression in erythroid cells.

Publication Title

Ldb1 regulates carbonic anhydrase 1 during erythroid differentiation.

Sample Metadata Fields

Specimen part

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accession-icon GSE14416
ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Interferon is effective at inducing complete remissions in patients with Chronic Myelogenous Leukemia (CML), and evidence supports an immune mechanism. Here we show that the Type I Interferons (alpha and beta) regulate expression of the Interferon consensus sequence binding protein (ICSBP) in bcr-abl transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of bcr-abl induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the Type I Interferons and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the anti-leukemic response of interferons suggest new strategies for immunotherapy of CML.

Publication Title

ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE1491
Identification of Inhibitors of Auxin Transcriptional Activation via Chemical Genetics in Arabidopsis
  • organism-icon Arabidopsis thaliana
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Approximately 2.5 mg dry Col-0 seedlings were surface sterilized and stratified for 2 days at 4degreesC in liquid media containing 1.5% sucrose (w/v) before being transferred to light with constant shaking at 100 rpm on an orbital shaker. After 7 days, the seedling clusters were subjected to the treatments for 1 hr followed by total RNA isolation using the RNAqueous kit (Ambion). Each treatment was performed in triplicate or quadruplicate. All labeling (Enzo) and hybridization (Affymetrix) procedures were performed as directed by the manufacturers. Raw probe intensities output by the Affymetrix MAS software were processed using the RMA algorithm to obtain an expression measure for each gene on each array.

Publication Title

Identification of inhibitors of auxin transcriptional activation by means of chemical genetics in Arabidopsis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE59037
Dissecting engineered cell types and enhancing cell fate conversion via CellNet
  • organism-icon Mus musculus
  • sample-icon 25 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.

Publication Title

Dissecting engineered cell types and enhancing cell fate conversion via CellNet.

Sample Metadata Fields

Specimen part

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accession-icon GSE49938
Re-specification of myeloid precursors from human pluripotent cells into engraftable multi-lineage progenitors
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Human pluripotent stem cells were differentiated into hematopoietic progenitors, which were then re-specified using defined transcription factors to resemble hematopoietic stem cells (HSC)

Publication Title

Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors.

Sample Metadata Fields

Specimen part

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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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