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GSE100176
Mus musculus
9 Downloadable Samples
Description
The heart uses primarily fatty acids and glucose for deriving energy. The majority of energy in the healthy heart derives from fat utilization, with the remainder coming primarily from the catabolism of glucose. Classical studies by Randle and colleagues describe the ability of the heart to switch its mode of utilization facilely and reversibly between glucose and fatty acids (myocardial glucose-fatty acid cycle or Randle cycle). However, under conditions of pathological stress, reliance of the heart on fatty acids decreases with a concomitant increase in reliance on glucose. It is unclear how such changes in metabolism regulate gene expression in the heart. Therefore, we examined how regulation of glycolysis at the level of phosphofructokinase modulates gene expression in the heart. We performed transcriptomic analysis of hearts from mice expressing either kinase-deficient phosphofructokinase 2 (GlycoLo) or phosphatase-deficient phosphofructokinase 2 (GlycoHi) under the control of the -MHC promoter, which restricted expression of the transgenes to the heart. Phosphofructokinase 2 only controls the ability of the myocyte to regulate abundance of a single metabolite, F-2,6-P2, which is an allosteric regulator of the rate-limiting and committed step in glycolysis. Parallel radiometric and metabolomic studies showed the expected increases or decreases in glycolytic flux along with diametrically opposite changes in fat metabolism, which is consistent with the myocardial glucose-fatty acid cycle. Transcriptomic analyses showed remarkable changes in gene transcription in these hearts, which indicates that glucose and/or fatty acid metabolism is a driver of transcriptional programs in the heart. Furthermore, glycolytic activity coordinately regulated numerous genes in the heart, including genes important for cardiac remodeling as well as genes regulating gluconeogenic and ancillary biosynthetic pathway activity. These findings reveal that glycolytic rate is a critical regulator of gene expression in the heart and can coordinate programs that modulate cardiac metabolism, growth, and hypertrophy.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Mast cells have been suggested to either promote or suppress tumor progression but the mechanisms underlying these outcomes are unclear. Here, we show that mice with a heterozygous mutation in the adenomatous polyposis coli gene (ApcMin/+) displayed reduced intestinal tumor burden and increased survival in the background of the chemokine decoy receptor ACKR2 deficiency (ACKR2-/-). The ACKR2-/-ApcMin/+ tumors showed increased infiltration of mast cells. In mast cell-deficient Sash (c-kitW-sh/W-sh) ACKR2-/-ApcMin/+ mice the survival advantage was lost as the tumors grew rapidly and adoptive transfer of mast cells reduced the tumor burden in these mice. The tumor burden is also increased in Rag2-/-ACKR2-/-ApcMin/+ mice and the protection is reconstituted by adoptively transferred CD8+ T-lymphocytes. Mast cells from ACKR2-/- mice expressed elevated levels of chemokine receptors CCR2 and CCR5 and are also efficient in antigen presentation and activation of CD8+ T-cells. Mast cell-derived leukotriene B4 is a critical mediator of CD8+ T-lymphocyte recruitment as the BLT1-/-ACKR2-/-ApcMin/+ mice are highly susceptible to intestinal tumor induced mortality. Taken together, these data demonstrate that chemokine mediated mast cell recruitment is essential for initiating LTB4/BLT1 regulated CD8+ T-cell homing and generation of effective anti-tumor immunity against intestinal tumor development.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
E-FABP expression in keratinocytes increase interferons, in particualur IFNlamda, expression, which activate P53, a critical tumor suppessor, to inhibit or prevent chemical-induced skin tumorigenesis.
Publication Title
Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
OVE26 (OVE) mice provide a useful model of advanced diabetic nephropathy (DN) with respect to albuminuria and pathologies. We showed that albuminuria, reduced GFR and interstitial fibrosis, which normally take 8-9 months to develop, are more advanced in uninephrectomized OVE mice within 10 weeks of surgery, at 4.5 months of age. The accelerated progression of renal damage, especially renal fibrosis in OVE-uni mice, was also identified at the gene expression level. The hepatic fibrosis/hepatic stellate cell activation pathway was by far the most significant Ingenuity canonical pathway identified by gene array in OVE-uni mice. Many inflammatory- and immune-related pathways were found among the top pathways up-regulated in OVE-uni kidneys, including acute-phase response signaling, leukocyte extravasation, IL6, IL10, IL12 signaling, TREM1 signaling, dendritic cell maturation and the complement system. These pathways were also dramatically up-regulated in 8-month-old OVE mice (GSE20636). Nephrectomized OVE mice are a much faster alternative model for studying advanced renal disease in diabetes.
Publication Title
Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 67 Downloadable Samples
Description
The Hippocampus Consortium data set provides estimates of mRNA expression in the adult hippocampus of 99 genetically diverse strains of mice including 67 BXD recombinant inbred strains, 13 CXB recombinant inbred strains, a diverse set of common inbred strains, and two reciprocal F1 hybrids.
Publication Title
Genetics of the hippocampal transcriptome in mouse: a systematic survey and online neurogenomics resource.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 93 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 2 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 108 Downloadable Samples
Description
Copy number variation (CNV) of DNA segments has recently been identified as a major source of genetic diversity, but a more comprehensive understanding of the extent and phenotypic effect of this type of variation is only beginning to emerge. In this study we generated genome-wide expression data from 6 mouse tissues to investigate how CNVs influence gene expression.
Publication Title
Segmental copy number variation shapes tissue transcriptomes.
Sample Metadata Fields
No sample metadata fields
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