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accession-icon GSE27625
Hepatic gene expression changes in aging and R--lipoic acid supplementation: Necroinflammatory phenotype, lipid synthesis regulation and circadian rhythms.
  • organism-icon Rattus norvegicus
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 months) and old (24 months) male Fischer 344 rats a diet with or without 0.2% (w/w) R--lipoic acid (LA) for two weeks. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profile. Results showed an increase in pro-inflammatory gene expression in the aging liver, with increased immune cell function and tissue remodeling genes, representing 45% of the age-related transcriptome changes. Increased inflammation was corroborated by increases in soluble ICAM1 levels with age. There were also observed age-related increases in transcription of genes related to lipid and cholesterol synthesis including Acetyl CoA Carboxylase (Acacb) and Fatty acid Synthase (Fasn). Supplementation of old animals with LA did not reverse this necro-inflammatory phenotype, yet limited age-associated hepatic dyslipidemia. Dietary LA further affected a small but concerted number of hepatic genes regardless of age. These included declines in lipid and bile synthesis genes. Decline in lipid synthesis genes was further corroborated by a decrease in Fasn and Acc protein levels. Intriguingly, LA also altered the expression of genes governing circadian rhythm, most notably Bmal1, Npas2, and Per2, which changed in a coordinated manner with respect to their rhythmic transcription. Thus, advanced age is associated with a necro-inflammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with energy metabolism and circadian rhythm regardless of age.

Publication Title

R-α-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon SRP102735
Expression profiles of restoration of BAP1 in a BAP1 deficient cell line
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins. Cell line UPMM3 contains a frameshift mutation in BAP1. Overall design: RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins

Publication Title

GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.

Sample Metadata Fields

Cell line, Subject

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accession-icon SRP090558
Interferon regulated genes in mouse intestine after irradiation and prophylactic Rig-I activation
  • organism-icon Mus musculus
  • sample-icon 45 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

As RIG-I activation induces potent IFN-I responses,we analyzed the role of IFN-I in intestinal tissue protection and prevention of GVHD. We performed RNA sequencing with tissue samples from SI of WT mice that received TBI -/+ previous 3pRNA treatment and -/+ antibody-mediated blockade of IFNAR. Application of 3pRNA before TBI resulted in a significant increase of IFN-inducible genes in the SI as compared to solely irradiated mice. Blockade of IFNAR signaling abrogated 3pRNA-mediated up-regulation of IFN-induced genes, demonstrating that RIG-I-induced gene-regulation depends on IFN-I. Overall design: Balb/c mice were solely irradiated (9Gy) (n=3), pretreated with Rig-I agonist 3pRNA prior (d-1) to irradiation (n=3) or pre-treated with 3pRNA (d-1) + anti-IFNaR1 blocking antibody (d-2) prior to irradiation (n=3). RNA from small intestines was isolated 12h after irradiation and used for RNA sequencing.

Publication Title

RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE23630
Modulation of gene expression in cultured human intestinal colon explants by probiotic bacteria
  • organism-icon Homo sapiens
  • sample-icon 17 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Background: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells.

Publication Title

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa.

Sample Metadata Fields

Specimen part

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accession-icon GSE51130
Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Original patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles.

Publication Title

Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP137054
Gene expression profiling of Smad2/3 cKO mice
  • organism-icon Mus musculus
  • sample-icon 32 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

Uterine double conditional inactivation of Smad2 and Smad3 in mice results in endometrial dysregulation, infertility, and uterine cancer. Smad2/3 cKO mice demonstrate abnormal expression of genes involved in inflammation, cell-cycle checkpoint, migration, steroid biosynthesis, and SMAD1/5-driven genes. We performed RNA-sequencing to identify the gene expression differences between the uterine epithelium of control and Smad2/3 cKO. To control for estrous cycle variations, the uterine epithelium was collected from mice at 0.5 dpc. Global gene expression profiles of Smad2/3 cKO versus control mice was analyzed. Our RNA sequencing analysis was performed at 6 weeks of life and already showed significant differences in migratory (Agr2,Slit2) and inflammatory (Ccl20, Crispld2) markers between Smad2/3 cKO and control mice. Overall design: Two group comparison: uterine epithelium of control and Smad2/3 cKO mice. We generated a conditional knockout of Smad2/3 in the uterus and demonstrated that Smad2/3 plays a critical role in the endometrium, with disruption resulting in pubertal-onset uterine hyperplasia and ultimately fatal uterine cancer.

Publication Title

Uterine double-conditional inactivation of <i>Smad2</i> and <i>Smad3</i> in mice causes endometrial dysregulation, infertility, and uterine cancer.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE87483
Dnmt3a restrains mast cell inflammatory responses
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

By utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.

Publication Title

&lt;i&gt;Dnmt3a&lt;/i&gt; restrains mast cell inflammatory responses.

Sample Metadata Fields

Sex, Specimen part, Treatment

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accession-icon GSE16744
Wild-type and COUP-TFI-/- newborn inner ear microarrays
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

In order to establish a list of candidate direct COUP-TFI gene targets in the inner ear, we analyzed the differential gene expression profiles of the wild-type and the COUP-TFI/ P0 inner ears.

Publication Title

Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI.

Sample Metadata Fields

Specimen part

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accession-icon GSE16970
Response of Pseudomonas aeruginosa PAO1 to low shear modeled microgravity
  • organism-icon Pseudomonas aeruginosa pao1
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Pseudomonas aeruginosa Array (paeg1a)

Description

Anticipating the risk for infectious disease during space exploration and habitation is a critical factor to ensure safety, health and performance of the crewmembers. As a ubiquitous environmental organism that is occasionally part of the human flora, Pseudomonas aeruginosa could pose a health hazard for the immuno-compromised astronauts. In order to gain insights in the behavior of P. aeruginosa in spaceflight conditions, two spaceflight-analogue culture systems, i.e. the rotating wall vessel (RWV) and the random position machine (RPM), were used. Microarray analysis of P. aeruginosa PAO1 grown in the low shear modeled microgravity (LSMMG) environment of the RWV compared to the normal gravity control (NG), revealed a regulatory role for AlgU (RpoE). Specifically, P. aeruginosa cultured in LSMMG exhibited increased alginate production and up-regulation of AlgU-controlled transcripts, including those encoding stress-related proteins. This study also shows the involvement of Hfq in the LSMMG response, consistent with its previously identified role in the Salmonella LSMMG- and spaceflight response. Furthermore, cultivation in LSMMG increased heat- and oxidative stress resistance and caused a decrease in the culture oxygen transfer rate. Interestingly, the global transcriptional response of P. aeruginosa grown in the RPM was similar to that in NG. The possible role of differences in fluid mixing between the RWV and RPM is discussed, with the overall collective data favoring the RWV as the optimal model to study the LSMMG-response of suspended cells. This study represents a first step towards the identification of specific virulence mechanisms of P. aeruginosa activated in response to spaceflight-analogue conditions, and could direct future research regarding the risk assessment and prevention of Pseudomonas infections for the crew in flight and the general public.

Publication Title

Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE73717
Gene expression profiling of mouse luminal uterine epithelium with knockout of ALK3
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

Bone morphogenetic proteins (BMPs) are transforming growth factor (TGF) family members that regulate the post-implantation and mid-gestation stages of pregnancy. In this study we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. To understand the role of ALK3 in the luminal uterine epithelium, we obtained the gene expression profiles of isolated luminal uterine epithelium from 3.5dpc control and Alk3 cKO mice.

Publication Title

Uterine ALK3 is essential during the window of implantation.

Sample Metadata Fields

Specimen part, Time

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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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