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GSE37386
Homo sapiens
23 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods for identifying protein-protein interactions have mostly been limited to tagged exogenous expression approaches. We now establish a rapid, robust and comprehensive method for finding interacting proteins using endogenous proteins from limited cell numbers. We apply this approach called Rapid IP-Mass Spectrometry of Endogenous proteins (RIME) to identify ER, FoxA1 and E2F4 interacting proteins in breast cancer cells. From small numbers of starting cells, we find a comprehensive collection of known ER, FoxA1 and E2F4 targets, plus a number of novel unexpected interactors. One of the most ER (and FoxA1) associated interactors is GREB1, an estrogen induced gene with almost no known function. We apply RIME, in parallel with ER ChIP-seq, to identify ER protein interactors and ER binding events from solid tumor xenografts, resulting in the validation of the ER-GREB1 interactions. Furthermore, we establish a method for identifying endogenous interacting proteins from solid primary breast cancer samples, whih we apply to validate ER interactions with GREB1 and additional co-factors. Mechanistically, we show that GREB1 is recruited with ER to the chromatin where it functions as an essential estrogen-mediated regulatory factor required for effective ER transcriptional activity. Our novel approach enables, for the first time, the ability for discovery and validation of protein-protein interactions in whole tissue and solid tumors, revealing significant insight into ER regulatory factors.
Publication Title
Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 192 Downloadable Samples
IlluminaHiSeq2000
Description
Exploring effect of progesterone/progestin treatment on gene expression Overall design: Two cell lines, three conditions (Full Media with E2, E2+ Progesterone, Full Media + R5020 Progestin)
Publication Title
Progesterone receptor modulates ERα action in breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice.
Publication Title
Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Identifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional ß cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development. Overall design: Analysis was carried out at 14.5 dpc embryonic pancreata and in 14.5 dpc embryonic pancreata that have been cultured in air to liquid interface cultures for two days (14.5 + 2). For the 14.5 dpc analysis wild type (14.5 wt) and S1pr2 null (14.5 S1pr2 null) pancreata were analyzed. For the analysis of cultured embryonic pancreata, conditions used were either standard conditions (14.5 + 2) or in the presence of 15 uM of JTE013 (14.5 + 2 + JTE) or in the presence of 15 uM of JTE013 and 50 ng/ml CTGF (14.5 + 2 + JTE + CTGF). Three biological replicates were used for each stage/condition for a total of 15 samples.
Publication Title
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.
Sample Metadata Fields
Cell line, Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Lactoferrin is a highly multifunctional protein. Indeed, it is involved in many physiological functions, including regulation of iron absorption and immune responses.
Publication Title
A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid <i>β</i> peptide toxicity in <i>Caenorhabditis elegans</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
The undifferentiated spermatogonial population of mouse testis is known to be functionally heterogeneous and contain both stem cells and committed progenitor cells. However, gene expression patterns marking these distinct cell fractions are poorly defined. We found that a subset of undifferentiated spermatogonia were marked by expression of a PDX1-GFP transgene but properties of these cells were unclear. Undifferentiated cells were therefore isolated from adult testes and separated according to expression of PDX1-GFP+ for gene expression analysis by RNA-seq. Our goal was to identify differentially expressed genes from PDX1-GFP+ vs PDX1-GFP- with that of known markers of stem and committed progenitor cells. Overall design: 4 independent sets of PDX1-GFP-positive and PDX1-GFP-negative undifferentiated spermatogonia were isolated by flow sorting from adult mouse testes.
Publication Title
Identification of dynamic undifferentiated cell states within the male germline.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 2 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In osteosarcoma patients, the development of metastases, often to the lungs, is the most frequent cause of death. To improve this situation, a deeper understanding of the molecular mechanisms governing osteosarcoma development and dissemination and the identification of novel drug targets for an improved treatment are needed. Towards this aim, we characterized osteosarcoma tissue samples compared to primary osteoblast cells using Affymetrix HG U133A microarrays.
Publication Title
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway.
Sample Metadata Fields
No sample metadata fields
View Samples