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GSE12209
Mus musculus
2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The adipocyte-derived hormone leptin maintains energy balance by acting on hypothalamic leptin receptors (Leprs) that trigger the signal transducer and activator of transcription 3 (Stat3). Although disruption of Lepr-Stat3 signaling promotes obesity in mice, other features of Lepr function, such as fertility, seem normal, pointing to the involvement of additional regulators. Here we show that the cyclic AMP responsive elementbinding protein-1 (Creb1)-regulated transcription coactivator-1 (Crtc1) is required for energy balance and reproductionCrtc1-/- mice are hyperphagic, obese and infertile. Hypothalamic Crtc1 was phosphorylated and inactive in leptin-deficient ob/ob mice; leptin administration increased amounts of dephosphorylated nuclear Crtc1. Dephosphorylated Crtc1 stimulated expression of the Cartpt and Kiss1 genes, which encode hypothalamic neuropeptides that mediate leptins effects on satiety and fertility. Crtc1 overexpression in hypothalamic cells increased Cartpt and Kiss1 gene expression, whereas Crtc1 depletion decreased it. Indeed, leptin enhanced Crtc1 activity over the Cartpt and Kiss1 promoters in cells overexpressing Lepr and these effects were disrupted by expression of a dominant-negative Creb1 polypeptide. As leptin administration increased recruitment of hypothalamic Crtc1 to Cartpt and Kiss1 promoters, our results indicate that the Creb1-Crtc1 pathway mediates the central effects of hormones and nutrients on energy balance and fertility.
Publication Title
The Creb1 coactivator Crtc1 is required for energy balance and fertility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We studied the role of the cAMP responsive factor CREB in promoting insulin resistance following its activation in adipose under obese conditions
Publication Title
Adipocyte CREB promotes insulin resistance in obesity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2000
Description
We report that after cancer cells are exposed to a transient pulse (5h) of the pro-inflammatory cytokine IFN?, they continue up-regulating genes in the antigen presentation pathway for days after abrogation of the original signal. We discovered that a new mechanism of cell-to-cell communication, cytokine catch-and-release, explains this surprising result. Overall design: Examination of IFN?-induced gene expression over multiple timepoints in mouse melanoma cells
Publication Title
Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals.
Publication Title
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The blockage of GABA-A ionotropic channels by means of gabazine is a widespread model of plasticity where the increased synaptic activity triggered by Gabazine leads to the up-regulation of a plethora of activity-dependent genes. Here, we sought to characterize the overall transcriptional response of GABA-A blocking of rat hippocampal organotypic cultures.
Publication Title
Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of WNT signaling upon knock-down (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFa as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the membrane localization, and thus function, of TGFa. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFa exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFa ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFa and GLI1 that enhances metastases. We suggest that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities. Overall design: CC14 and CC36, two primary colon cancer cells, were treated with control or shTMED9 expressing lentivirus. In addition, CC14 cells were also treated with shTMED3 expressing lentivirus. All the experiments were run in triplicates totaling 15 Samples.
Publication Title
The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Publication Title
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Postnatal handling in rodents leads to decreased anxiety-like behavior in adulthood. We used microarrays to look at gene expression differences in the CA1 region of the hippocampus in female mice subjected to postnatal handling compared to controls.
Publication Title
Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Publication Title
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Genetically identical inbred mice exhibit substantial stable individual variability in exploratory behavior. We used microarrays to look at gene expression differences in the hippocampus in female mice separated by stable differences in exploratory behavior
Publication Title
Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.
Sample Metadata Fields
No sample metadata fields
View Samples