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GSE61904
Mus musculus
7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Existing controversy regarding the importance of AMP-activated protein kinase (AMPK) in fatty acid (FA) oxidation in skeletal muscle with contraction/exercise may to some extent pertain to redundant AMPK1 signaling. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO) we hypothesized that FA utilization would be impaired in skeletal muscle. Calorimetric analysis showed a similar respiratory exchange ratio (RER) of AMPK WT and mdKO mice when fed normal chow, a high fat diet or with prolonged fasting. Though, in vivo treadmill exercise at the same relative intensity induced a higher RER in mdKO mice compared to WT (WT=0.81; mdKO=0.87; p<0.01) indicating a decreased utilization of FA. Ex vivo incubation of soleus muscle revealed that basal and contraction-induced FA oxidation was impaired in mdKO mice, suggesting that the increased RER during in vivo running exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 and FABPpm (by 17-40%) together with abolishment of TBC1D1 Ser237 phosphorylation in mdKO mice, may result in lower FA transport capacity and FA transport protein translocation to sarcolemma, respectively. In summary this study shows that the catalytically active AMPK subunits are required for normal stimulation of FA utilization during exercise and contractions.
Publication Title
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To directly address the function of myeloid CD13 we created a CD13 null mouse and assessed the responses of purified primary macrophages or dendritic cells from wild type and CD13 null animals in cell assays and inflammatory disease models where CD13 has been previously implicated. We find that mice lacking CD13 develop normally with normal hematopoietic profiles. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation and antigen presentation that we tested, but may contribute to adhesion to endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 wild type and null macrophages argue against compensatory mechanisms. Analysis of the dataset with Ingenuity Pathway Analysis software did not suggest that loss of CD13 resulted in a purturbation of any specific biological pathways, processes or networks. Therefore, while CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of both normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis or myeloid cell function.
Publication Title
CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The normally virulent type-I RH parasite is rendered avirulent when lacking ROP5. The avirulent phenotype is a consequence of interaction with the host innate immune system. We sought to understand if ROP5 alters host gene expression in order to escape host defenses. We saw no gene expression differences between host cells infected with wt (RHku80) or RHku80rop5 parasites. We have included uninfected HFF samples that were harvested in parallel with the infected samples.
Publication Title
The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Background: The ability of an organism to repair damages to DNA is inextricably linked to aging and cancer. We have characterized and compared the transcriptome of C. elegans mutants deficient in DNA base excision repair, nucleotide excision repair or both to elucidate the transcriptional changes incurred by the reduction of these repair pathways.
Publication Title
A two-tiered compensatory response to loss of DNA repair modulates aging and stress response pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, RNA-seq analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Skipping of lipin1 exon 7 is controlled by SRSF10-regulated cis-element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1a mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin1a and thus promotes adipocyte differentiation. Indeed, lipin1a expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing. Overall design: RNA-seq for wide type (WT) and SRSF10-deficient (KO) mouse MEF cells
Publication Title
SRSF10 regulates alternative splicing and is required for adipocyte differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The glucocorticoid receptor overexpression in early life is sufficient to alter gene expression patterns for the rest of the animal's life.
Publication Title
Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization.
Sample Metadata Fields
Sex, Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The nematode Caenorhabditis elegans has been used extensively to study responses to DNA damage. In contrast, little is known about DNA repair in this organism. C. elegans is unusual in that it encodes few DNA glycosylases and the uracil-DNA glycosylase (UDG) encoded by the ung-1 gene is the only known UDG. C. elegans could therefore become a valuable model organism for studies of the genetic interaction networks involving base excision repair (BER). As a first step towards characterization of BER in C. elegans, we show that the UNG-1 protein is an active uracil-DNA glycosylase. We demonstrate that an ung-1 mutant has reduced ability to repair uracil-containing DNA but that an alternative Ugi-inhibited activity is present in ung-1 nuclear extracts. Finally, we demonstrate that ung-1 mutants show altered levels of apoptotic cell corpses formed in response to DNA damaging agents. Increased apoptosis in the ung-1 mutant in response to ionizing radiation (IR) suggests that UNG-1 contributes to repair of IR-induced DNA base damage in vivo. Following treatment with paraquat however, the apoptotic corpse-formation was reduced. Gene expression profiling suggests that this phenotype is a consequence of compensatory transcriptomic shifts that modulate oxidative stress responses in the mutant and not an effect of reduced DNA damage signaling.
Publication Title
Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genetic susceptibility underlies the pathogenesis of cancer. Through genome-wide association studies, we and others have previously identified a novel susceptibility gene, TNFRSF19, which encodes an orphan member of the TNF receptor superfamily, to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation and NPC development. However, unlike most of TNF receptors, TNFRSF19 is not involved in NF-B activation or associated with TRAF proteins. By affinity purification, we identified TGF receptor type-I (TRI) as a specific binding partner for TNFRSF19. TNFRSF19 binds to the kinase domain of TRI in the cytoplasm and thereby blocks the Smad2/3 association with TRI and subsequent signal transduction. Ectopic expression of TNFRSF19 in normal epithelial cells confers resistance to the cell cycle block induced by TGF, whereas knockout of TNFRSF19 in NPC cells unleashes a potent TGF response characterized by upregulation of Smad2/3 phosphorylation and TGF target gene transcription. Furthermore, elevated TNFRSF19 expression correlates with reduced TGF activity and poor prognosis in NPC patients. Our data reveal that gain-of-function of TNFRSF19 in NPC represents a mechanism by which tumor cells evade the growth-inhibitory action of TGF.
Publication Title
TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 32 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the frontline of immune defense against HIV infection. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we have performed a comparative analysis of host gene expression in the lung and GI mucosa in response to SIV infection and antiretroviral therapy.
Publication Title
Enhanced innate antiviral gene expression, IFN-α, and cytolytic responses are predictive of mucosal immune recovery during simian immunodeficiency virus infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The goals of this study aim to reveal functional and phenotypic diversity of leukemia-associated macrophages in response to the microenvironmental cues in mouse T cell acute lymphoblastic leukemia Overall design: Compare Transcriptomes of macrophages in T cell acute leukemia which are suggested as leukemia-associated macrophages (LAMs) with homeostasis
Publication Title
Organ-specific microenvironment modifies diverse functional and phenotypic characteristics of leukemia-associated macrophages in mouse T cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
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