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GSE39976
Homo sapiens
26 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Approximately 5% of all breast cancers can be attributed to an inherited mutation in one of two cancer susceptibility genes, BRCA1 and BRCA2. We searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from non-carriers based on differences in expression profiling. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers. We identified 137 probe sets in BRCA1 carriers and 1345 in BRCA2 carriers with differential gene expression. Gene Ontology analysis revealed that most of these genes relate to regulation pathways of DNA repair processes, cell cycle regulation and apoptosis. Real-time PCR was performed on the 36 genes which were most prominently differentially expressed in the microarray assay; 21 genes were shown to be significantly differentially expressed in BRCA1 or BRCA2 mutation carriers as compared to controls (p<0.05). Based on a validation study with 40 mutation carriers and 17 non-carriers, a multiplex model that included six or more coincidental genes of 18 selected genes was constructed in order to predict the risk of carrying a mutation. The results using this model showed sensitivity 95% and specificity 88%. In summary, our study provides insight into the biological effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation induced DNA damage. We also suggest a set of 18 genes that can be used as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes.
Publication Title
Determination of molecular markers for BRCA1 and BRCA2 heterozygosity using gene expression profiling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TREM-2 has been described to be a phagocytic receptor. We assessed the influence of TREM-2 on gene expression in alveolar macrophages (AM)
Publication Title
The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 53 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 40 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
While the mouse cornea has been well characterized morphologically, the transcriptional changes have not been described in detail. To characterize the genes, pathways, and transcriptional regulators involved in mouse cornea development and aging, we isolated whole cornea from wildtype CB6 mice at several developmental timepoints and every 6 months in the adult. Corneal epithelium and stroma were isolated at one timepoint to provide insights into the genes that are unique to each tissue.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Ehf is a transcriptional regulator that is highly expressed and enriched in corneal epithelium. To gain insights into the role of Ehf in the corneal epithelium, we performed siRNA knockdown of Ehf in primary human corneal epithelial cells.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To understand the gene-regulatory role of H19 in corneal epithelial cells and to explore whether CLIM activation of H19 might account for non-cell proliferation effects of CLIM, we used siRNA to knock down H19 in primary human corneal epithelial cells. Microarray gene expression analysis revealed that 1,249 genes are down regulated 1.5 fold or more by siH19 compared to scramble control, and that 944 genes are up regulated
Publication Title
Cofactors of LIM Domains Associate with Estrogen Receptor α to Regulate the Expression of Noncoding RNA H19 and Corneal Epithelial Progenitor Cell Function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cofactors of LIM domain proteins (CLIM1 and CLIM2) are widely expressed transcriptional cofactors that are recruited to gene regulatory regions by DNA-binding proteins, including LIM domain transcription factors. In the cornea, epithelial specific expression of a dominant negative (DN) CLIM under the Keratin 14 (K14) promoter causes blistering, inflammation, epithelial hyperplasia and neovascularization, followed by epithelial thinning and subsequent epidermal-like differentiation of the cornea epithelium. This phenotype resembles aspects of limbal stem cell deficiency, suggesting that CLIM proteins may be involved in regulating cornea stem cell maintenance. Consistent with this notion, the K14-DN-Clim cornea epithelium has fewer progenitor cells, and altered proliferation dynamics during epithelial development. Differentially regulated genes in DN-CLIM corneas include those in pathways crucial for stem cell maintenance and regulation of proliferation. In vivo ChIP-Seq experiments in the cornea epithelium show that CLIM associates with DNA regulatory elements containing binding sites for HLH and other non-LIM homeodomain factors, and that many genes that are highly expressed in the limbal epithelium, as well as genes with known roles in stem cell maintenance, are directly regulated by CLIM cofactors. DN-CLIM decreases the expression of Wnt inhibitors, including the direct target Wnt5a, causing increased Wnt signaling in the limbal region of DN-CLIM corneas. Together our results indicate that CLIMs regulate cornea stem cell maintenance by controlling Wnt activity and suggest the possibility that this pathway may be altered in limbal stem cell deficiency.
Publication Title
Cofactors of LIM Domains Associate with Estrogen Receptor α to Regulate the Expression of Noncoding RNA H19 and Corneal Epithelial Progenitor Cell Function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Branching morphogenesis of the mammary gland is driven by the highly motile terminal end bud (TEB) throughout pubertal development. The stem cell enriched, proliferative TEB branches as it invades the mammary fat pad to create a complex network of ducts. The gene expression programs specific to the TEB and the differentiated duct are poorly understood. We conducted a time course analysis of gene expression in the TEB and duct throughout branching morphogenesis. Additionally, we determined the gene regulatory networks coordinated by the Co-factor of LIM domains (CLIM/LDB) transcriptional regulators and determined an essential function for CLIMs in branching morphogenesis by maintaining basal mammary epithelial stem cells and promoting cell proliferation.
Publication Title
The co-factor of LIM domains (CLIM/LDB/NLI) maintains basal mammary epithelial stem cells and promotes breast tumorigenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). However, it is still unknown whether and how epithelial plasticity is kept in check in epithelial cells during development. Here we show that restricting the EMT of mammary epithelial cells by transcription factor Ovol2 is required for proper morphogenesis and regeneration. Deletion of Ovol2 blocks mammary ductal morphogenesis, depletes stem/progenitor cell reservoirs, and leads epithelial cells to undergo EMT in vivo to become non-epithelial cell types. Ovol2 directly represses myriad EMT inducers and its absence switches response to TGF-beta from growth arrest to EMT. Furthermore, forced expression of the repressor isoform of Ovol2 is able to reprogram metastatic breast cancer cells from a mesenchymal to an epithelial state. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity in development and cancer.
Publication Title
Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2 transcriptional repressor.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples