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GSE38392
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma.
Publication Title
Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes ewing sarcoma growth.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPAR/ mice to allow exploration of the specific contribution of PPAR. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPAR agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPAR-dependent manner, emphasizing the importance of PPAR in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPAR had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPAR.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Populus tremula x populus alba
- 25 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We study the effect of nitrogen limitation on the growth and development of poplar roots. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes driven by low nitrogen in the growth media. We report the effect of nitrogen limitation on the growth and development of poplar roots. Low nitrogen concentration led to increased root elongation followed by lateral root proliferation and finally increased root biomass. These morphological responses correlated with high and specific activation of genes encoding regulators of cell cycle and enzymes involved in cell wall biogenesis, growth and remodeling. Comparative analysis of poplar and Arabidopsis root transcriptomes under nitrogen deficiency indicated many similarities and diversification in the response in the two species. A reconstruction of genetic regulatory network (GRN) analysis revealed a sub-network centered on a PtaNAC1-like transcription factor. Consistent with the GRN predictions, root-specific upregulation of PtaNAC1 in transgenic poplar plants increased root biomass and led to significant changes in the expression of the connected genes specifically under low nitrogen. PtaNAC1 and its regulatory miR164 showed inverse expression profiles during response to LN, suggesting of a micro RNA mediated attenuation of PtaNAC1 transcript abundance in response to nitrogen deprivation.
Publication Title
Nitrogen deprivation promotes Populus root growth through global transcriptome reprogramming and activation of hierarchical genetic networks.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defining the molecular character of the developing and adult kidney podocyte.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of fluorescent activated cell sorting (FACS) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in FACS isolated components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone.
Publication Title
Defining the molecular character of the developing and adult kidney podocyte.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Notch receptors direct the differentiation of T helper (Th) cell subsets, but their influence on regulatory T (TR) cell responses is obscure. Interruption of Notch signaling in TR cells resulted in a super-regulatory phenotype, with suppression of TR cell Th1 programming and apoptosis as well as Th1 cell responses in systemic inflammation. In contrast, gain of function Notch1 signaling in TR cells resulted in lymphoproliferation, dysregulated Th1 responses and autoimmunity. To determine mechanisms by which Notch signaling may alter TR cell function, we compared the transcriptional profiles of splenic TR cells of Foxp3EGFPCre mice with those of Foxp3EGFPCreR26N1c/N1c (gain of function Notch signaling), Foxp3EGFPCreRBPJ/ (loss of function canonical Notch signaling), and Foxp3EGFPCreR26N1c/N1cRBPJ/ mice (gain of function/canonical loss of function Notch signaling).
Publication Title
Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of fluorescent activated cell sorting (FACS) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in FACS isolated components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone
Publication Title
Defining the molecular character of the developing and adult kidney podocyte.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
In adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multi-potency. We also show that, within the bulge, there are two distinct populations, one of which maintains basal lamina contact and temporally precedes the other, which is suprabasal and arises only after the start of the first postnatal hair cycle. This spatial distinction endows them with discrete transcriptional programs, but surprisingly, both populations are growth inhibited in the niche but can self-renew in vitro and make epidermis and hair when grafted. These findings suggest that the niche microenvironment imposes intrinsic stemness features without restricting the establishment of epithelial polarity and changes in gene expression.
Publication Title
Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of fluorescent activated cell sorting (FACS) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in FACS isolated components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone.
Publication Title
Defining the molecular character of the developing and adult kidney podocyte.
Sample Metadata Fields
Sex
View Samples