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accession-icon GSE74245
Activation of the pyruvate dehydrogenase complex dictates tumour progression in prostate cancer
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina MouseRef-8 v2.0 expression beadchip

Description

Metabolism in cancer serves to provide energy and key biomolecules that sustain cell growth, a process that is frequently accompanied by decreased mitochondrial use of glucose. Importantly, metabolic intermediates including mitochondrial metabolites are central substrates for post-translational modifications at the core of cellular signalling and epigenetics. However, the molecular means that coordinate the use of mitochondrial metabolites for anabolism and nuclear protein modification are poorly understood. Here, we unexpectedly found that genetic and pharmacological inactivation of Pyruvate Dehydrogenase A1 (PDHA1), a subunit of pyruvate dehydrogenase complex (PDC) that regulates mitochondrial metabolism16 inhibits prostate cancer development in different mouse and human xenograft tumour models. Intriguingly, we found that lipid biosynthesis was strongly affected in prostate tumours upon PDC inactivation. Mechanistically, we found that nuclear PDC controls the expression of Sterol regulatory element-binding transcription factor (SREBF) target genes by mediating histone acetylation whereas mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated effort to sustain anabolism. In line with the oncogenic function of PDC in prostate cancer, we find that PDHA1 and the PDC activator, Pyruvate dehydrogenase phospatase 1 (PDP1), are frequently amplified and overexpressed at both gene and protein level in these tumours. Taken together, our findings demonstrate that both mitochondrial and nuclear PDC sustains prostate tumourigenesis by controlling lipid biosynthesis thereby pointing at this complex as a novel target for cancer therapy.

Publication Title

Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE478
Alveoli loss during caloric restriction time course
  • organism-icon Mus musculus
  • sample-icon 25 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

Pulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.

Publication Title

Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.

Sample Metadata Fields

Time

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accession-icon GSE484
Alveoli septation inhibition and protection
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

It has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.

Publication Title

DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP125739
Expression levels of genes of LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen, 3 days after antigenic re-challenge
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We performed RNA-Seq and compared expression levels of genes of reactivated LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen of LCMV.GP61-80 primed C57BL/6 mice. Cells were isolated 3 days after antigenic re-challenge Overall design: C57BL/6 mice were primed at day 0 with LCMV.GP61-80-NP-MSA + poly(I:C) and immunized again at day 14 with LCMV.GP61-80 + poly(I:C). 60 days later, C57BL/6 mice were boosted with LCMV.GP61-80-NP-MSA + poly(I:C) and 3 days after the boost, LCMV specific CD4 T cells were isolated from BM and spleen

Publication Title

Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.

Sample Metadata Fields

Age, Specimen part, Cell line, Subject

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accession-icon GSE64696
Gene expression of Th cells, macrophages and monocytes derived from WT and Tbx21-/- Th cell-induced colitis
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

We compared gene expression profiles of Th cells, macrophages and monocytes isolated from the inflamed colon of colitis induced by the transfer of WT versus Tbx21-/- Th cells in Rag1-/- recipients.

Publication Title

T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.

Sample Metadata Fields

Specimen part

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accession-icon SRP167958
MicroRNA-31 reduces the motility of proinflammatory T helper 1 lymphocytes
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We performed total RNA-Seq of murine Th1 cells which were four times reactivated in vitro in the presence of irradiated APC'srepeatedly activated in vitro. Overall design: CD4+CD62Lhi (naive) cells were isolated from C57BL/6 mice, activated with aCD3 and aCD28 an cultured under Th1 polarizing conditions in the presence of irradiated APCs. Every sixth day cells were harvested, restimulated with aCD3 and aCD28 and cultured under Th1 polarizing conditions in the presence of irradiated APCs APCs. After four rounds of restimulation, total RNA was extracted and cDNA libraries for total RNA sequencing were generated using “TruSeq® Stranded Total RNA Library” kit (Illumina, San Diego, CA, USA).

Publication Title

MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE24071
HMGA2 overexpression
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3 untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (Hmga2 mice) with a 3UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the Hmga2+ cells. In summary, our results showed that the overexpression of a 3UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.

Publication Title

3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice.

Sample Metadata Fields

Specimen part

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accession-icon GSE33654
Gene expression from healthy male and female porcine aortic valve leaflets
  • organism-icon Sus scrofa
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Porcine Genome Array (porcine)

Description

Calcific aortic valvular disease (CAVD) is characterized by sclerosis of the aortic valve leaflets and recent clinical studies have linked several other risk factors to this disease, including male sex. In this study we examined potential sex-related differences in gene expression profiles between porcine male and female valvular interstitial cells (VICs) to explore possible differences in CAVD propensity on the cellular level.

Publication Title

Sex-related differences in gene expression by porcine aortic valvular interstitial cells.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE37415
Phloridzin reduces blood glucose levels and alters hepatic gene expression in normal BALB/c mice
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

We previously showed that a diet containing phloridzin suppressed the blood glucose levels in streptozotocin-induced diabetic mice most likely by inhibiting glucose absorption from the small intestine. In this study, we showed that 0.5% and 1% phloridzin diets significantly reduce the blood glucose levels in healthy normal BALB/c mice after 7 days of feeding.

Publication Title

Phloridzin reduces blood glucose levels and alters hepatic gene expression in normal BALB/c mice.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE38067
Hepatic gene expression in streptozotocin-induced diabetic mice fed a quercetin diet
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury.

Publication Title

Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.

Sample Metadata Fields

Sex, Specimen part

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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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