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SRP045204
Homo sapiens
4 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
HITS-CLIP of control and transfected cells to find direct targetting of miR-200 family to mRNA
Publication Title
Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion.
Sample Metadata Fields
No sample metadata fields
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- 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). Recent studies suggest that EMT endows differentiated epithelial cells with stem cell traits, posing the interesting question of how epithelial plasticity is properly restricted to ensure epithelial differentiation during tissue morphogenesis. Here we identify zinc-finger transcription factor Ovol2 as a key suppressor of EMT of mammary epithelial cells. Epithelia-specific deletion of Ovol2 completely arrests mammary ductal morphogenesis, and depletes epithelial stem/progenitor cell reservoirs. Further, Ovol2-deficient epithelial cells undergo EMT in vivo to become non-epithelial cell types, and that Ovol2 directly represses key EMT inducers such as Zeb1 and regulates stem/progenitor cell responsiveness to TGF-beta. We also provide evidence for a suppressive role of Ovol2 in breast cancer progression. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity to balance stemness with epithelial differentiation 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