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accession-icon GSE82111
Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology.
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets. Immortalized cell lines recapitulate NR biology very poorly and primary cultures are laborious and require a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology since technical uncertainty early in drug development is the cause of many preclinical drugs not reaching the clinic. Here, we studied whether organoids, mini-organs derived from the respective tissues stem cells, can serve as a novel (preclinical) model system to study NR biology and targeteability. We characterized mRNA expression profiles of the NR superfamily in mouse liver, ileum, and colon organoids. NR mRNA expression patterns were similar to the respective tissues, indicating their suitability for NR research. Metabolic NRs Fxr, Lxr, Lxr, Ppar, and Ppar were responsive to ligands in an NR-dependent fashion, as demonstrated by regulation of expression and binding to endogenous target genes. Transcriptome analyses of wildtype colonic organoids stimulated with Rosiglitazone showed that lipid metabolism was the highest significant changed function, greatly mimicking the known function of PPARs and Rosiglitazone in vivo. In conclusion, our results demonstrate that organoids constitutes a versatile and promising in vitro system to study NR biology and targeteability.

Publication Title

Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology.

Sample Metadata Fields

Treatment

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accession-icon GSE50820
Expression data from MCF7 and BT474 cell lines after long term estrogen deprivation culture
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

MCF7 and BT474 cell lines were exposed to LTED culture for 0 and 2 days, 6 weeks and 10 months and monitored for changes in gene expression

Publication Title

Clinical instability of breast cancer markers is reflected in long-term in vitro estrogen deprivation studies.

Sample Metadata Fields

Cell line, Treatment, Time

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accession-icon GSE38261
Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

To determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes

Publication Title

Distinct transcriptional signatures of bone marrow-derived C57BL/6 and DBA/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes.

Sample Metadata Fields

Specimen part

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accession-icon GSE11497
Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In mammals, resident dermal macrophages (Ms) are subverted by Leishmania (L.) amazonensis amastigotes as host cells permissive for parasite multiplication. These Leishmania are living within a communal parasitophorous vacuole (PV) and are expected to trigger unique M transcriptional signatures. We performed a transcription profiling of mouse Ms harboring amastigotes to get insights into their reprogramming as host cells for parasite multiplication. BALB/c mouse bone marrow-derived Ms were either loaded or not with four amastigotes on average. Twenty four hours later, when amastigotes multiply, total RNA from M cultures was prepared, amplified and hybridized onto Affymetrix Mouse430_2 GeneChips. The outcome recorded a total of 1,248 probe-sets showing significant differential expression. Comparable fold-change values for a handful of genes were obtained between Affymetrix technology and the more sensitive RTqPCR method. Ingenuity Pathway Analysis software pinpointed the up-regulation of the sterol biosynthesis pathway (P-value = 1.31e-02) involving several genes (1.95 to 4.30 fold-change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signaling. Our findings suggest that amastigotes exploit the M lipid and polyamine pathways to multiply efficiently, and induce a counter-inflammatory environment to expand their dermis niche.

Publication Title

Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE76163
Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

Sample Metadata Fields

Sex, Specimen part, Treatment, Subject, Time

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accession-icon GSE76162
Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [mouse]
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.

Publication Title

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

Sample Metadata Fields

Sex, Specimen part, Treatment, Time

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accession-icon GSE76161
Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [human]
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.

Publication Title

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

Sample Metadata Fields

Sex, Specimen part, Treatment, Subject, Time

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accession-icon GSE30626
Candidate pathways for promoting differentiation and quiescence of oligodendrocyte progenitor-like cells in glioblastoma
  • organism-icon Mus musculus
  • sample-icon 34 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The mature CNS contains PDGFRA+ oligodendrocyte progenitor cells (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.

Publication Title

Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma.

Sample Metadata Fields

Specimen part

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accession-icon GSE30016
Comparison of polysomal profiles of murine adult normal, tumor, and recruited olig2 cells
  • organism-icon Mus musculus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin

Publication Title

Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.

Sample Metadata Fields

Specimen part

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accession-icon SRP081314
Expression profiling of cochlear ducts from P8 Gfi1cre/+ and Gfi1+/+ mice
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

The Gfi1-Cre mouse is commonly used for conditional hair cell-specific gene deletion/activation in the inner ear. However, we have shown that these mice produce a pattern of recombination that is not strictly limited to hair cells, and that Gfi1cre/+ mice exhibit an early onset progressive hearing loss as compared with their wildtype littermates. Here we performed a transcriptome analysis of Gfi1cre/+ and Gfi1+/+ cochlea to detect potential changes in gene expression that could contribute to their hearing loss phenotype, or that could potentially confound downstream analysis of conditional gene deletion using these mice. Overall design: Trancriptome profiles of P8 cochlear duct from mice of two genotype - Gfi1cre/+ and Gfi+/+ controls - were measured. Gene expression levels were recorded in independent triplicates using polyA-enriched RNA-seq

Publication Title

Gfi1<sup>Cre</sup> mice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells.

Sample Metadata Fields

Specimen part, Cell line, 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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