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GSE103363
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
Publication Title
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is required to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. In order to study the impact of ING1-GADD45a on gene expression, we compared the expression profile of wildtype mouse embryonic fibroblasts (MEFs) with Ing1- and Gadd45a- single- or double-knockout (DKO) MEFs. Overall design: Gene expression profiling in all 4 genotypes of undifferentiated MEFs in triplicates.
Publication Title
Impaired DNA demethylation of C/EBP sites causes premature aging.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.
Publication Title
Fibronectin regulates Wnt7a signaling and satellite cell expansion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Satellite cells are responsible for the long-term regenerative capacity of adult skeletal muscle. The diminished muscle performance and regenerative capacity of aged muscle is thought to reflect progressive fibrosis and atrophy. Whether this reduction in muscle competency also involves a diminishment in the intrinsic regulation of satellite cell self-renewal remains unknown.
Publication Title
Inhibition of JAK-STAT signaling stimulates adult satellite cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. Overall design: Duct cells were isolated from mice of 3 different genotypes and duct cells from 3 mice of each genotype were sequenced. For the put back experiments, control retrovirus and that expressing Brg1 were transdcued in Brg1 null IPMN mouse cell line.
Publication Title
Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The NF1 tumor suppressor encodes a RAS GTPase-Activating Protein (RasGAP). Accordingly, deregulated RAS signaling underlies the pathogenesis of NF1-mutant cancers. However, while various RAS effector pathways have been shown to function in these tumors, it is currently unclear which specific proteins within these broad signaling pathways represent optimal therapeutic targets. Here we identify mTORC1 as the key PI3K pathway component in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. We also report that combined mTORC1/MEK inhibition is required to promote tumor regression in animal models, but only when the inhibition of both pathways is sustained. Transcriptional profiling studies were also used to establish a predictive signature of effective mTORC1/MEK inhibition in vivo. Within this signature, we unexpectedly found that the glucose transporter gene, GLUT1, was potently suppressed but only when both pathways were effectively inhibited. Moreover, unlike VHL and LKB1 mutant cancers, reduction of 18F-FDG uptake measured by FDG-PET required the effective suppression of both mTORC1 and MEK. Together these studies identify optimal and sub-optimal therapeutic targets in NF1-mutant malignancies and define a non-invasive means of measuring combined mTORC1/MEK inhibition in vivo, which can be readily incorporated into clinical trials.
Publication Title
Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The canonical role of eEF1A is to deliver the aminoacyl tRNA to the ribosome, we have used the yeast model system to investigate further roles for this protein.
Publication Title
Inappropriate expression of the translation elongation factor 1A disrupts genome stability and metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 53 Downloadable Samples
- IlluminaHiSeq2000
Description
The intention was to detect genes that are determining trastuzumab efficiency in HER2-positive breast cancer cell lines with different resistance phenotypes. While BT474 should be sensitive to the drug treatment, HCC1954 is expected to be resistant due to a PI3K mutation. The cell line BTR50 has been derived from BT474 and was cultured to be resistant as well. Based on RNA-Seq data, we performed differential expression analyses on these breast cancer cell lines with and without trastuzumab treatment. In detail, five separate tests were performed, namely resistant cells vs. wild type, i.e. HCC1954 and BTR50 vs. BT474, respectively, and untreated vs. drug treated cells. The significant genes of the first two tests should contribute to resistance. The significant genes of the test BT474 vs. its drug treated version should contribute to the trastuzumab effect. To exclude false positives from the combined gene set (#64), we removed ten genes that were also significant in the test BTR50 vs. its drug treated version. This way we ended up with 54 genes that are very likely to determine trastuzumab efficiency in HER2-positive breast cancer cell lines. Overall design: mRNA profiles of human breast cancer cell lines were generated by deep sequencing using Illumina HiSeq 2000. The cell lines BT474 and HCC1954 were analyzed with and without trastuzumab treatment. HCC1954 is known to be trastuzumab resistant. Additionally, the cell line BTR50 was generated as resistant version of BT474, and was analyzed with and without trastuzumab as well.
Publication Title
mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ERG overexpression was conducted in stably transfected K562 cell line with a tet-on inducible plasmid habouring ERG3. Prolonged induction of ERG (8 days) produced spindle cell shape changes whereas non-induced cells retained the round morphology. In oder to determine the genes responsible for inducing cell shape changes, a genome wide transcriptional screen was conducted.
Publication Title
ERG induces a mesenchymal-like state associated with chemoresistance in leukemia cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
Publication Title
Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.
Sample Metadata Fields
Age, Specimen part
View Samples