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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 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 GSE77087
Nasopharyngeal microbiota, host transcriptome and disease severity in children with respiratory syncytial virus infection
  • organism-icon Homo sapiens
  • sample-icon 104 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.

Publication Title

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

Sample Metadata Fields

Sex, Specimen part, Disease, Race

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accession-icon GSE67059
Whole Blood Transcriptional Profiling Differentiates Between Asymptomatic and Symptomatic Human Rhinovirus Detection in Children
  • organism-icon Homo sapiens
  • sample-icon 151 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V3.0 expression beadchip

Description

Human rhinoviruses (HRV) are among the most common causes of respiratory infections in humans but can be frequently detected also in asymptomatic subjects. We evaluated the value of gene expression profiles to differentiate asymptomatic detection from symptomatic HRV infection in children.

Publication Title

Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.

Sample Metadata Fields

Sex, Age, Specimen part, Disease, Disease stage, Race

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accession-icon SRP133497
Gain-of-function mutations in DNMT3A in patients with paraganglioma
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon

Description

Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq

Publication Title

Gain-of-function mutations in DNMT3A in patients with paraganglioma.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP164908
Tumor-infiltrating immune cells of young and aged mice
  • organism-icon Mus musculus
  • sample-icon 74 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

Macrophages, dendritic cells, conventional CD4+ T cells, CD8+ T cells, and regulatory T cells isolated from mouse colon cancer model MC38 tumors implanted subcutaneously to young (3 month) and aged (12 month) mice were sequenced using ImmGen's standard ultra-low input RNA-seq pipeline, in order to study age-dependent differences in intraltumoral immune cell functions and their impact on tumor control Overall design: Samples collected at the Center for Systems Biology at Mass General Hospital, shipped frozen to a central location, and sequenced using ImmGen's standard RNA-seq pipeline

Publication Title

Age-related tumor growth in mice is related to integrin α 4 in CD8+ T cells.

Sample Metadata Fields

Age, Specimen part, Cell line, Subject

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accession-icon SRP028873
Anopheles gambiae strain:SUA2La Transcriptome or Gene expression
  • organism-icon Anopheles gambiae
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II, Illumina HiSeq 2000

Description

Anopheles gambiae antennal and palpal transcriptome expression profiles (male and female)

Publication Title

Transcriptome profiling of chemosensory appendages in the malaria vector Anopheles gambiae reveals tissue- and sex-specific signatures of odor coding.

Sample Metadata Fields

Sex, Specimen part, Cell line

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accession-icon GSE32373
Gene expression analysis of OX40-triggered mouse Treg
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina MouseRef-8 v2.0 expression beadchip

Description

Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor.

Publication Title

Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells.

Sample Metadata Fields

No sample metadata fields

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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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Developed by the Childhood Cancer Data Lab

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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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