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GSE54126
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- Mus musculus
- 20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/2-deficient epidermal cells fail to undertake alpha-catenindriven actin cytoskeletal reorganization and adhesive maturation, and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations as well as defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-a-catenin sequential repression and highlight novel functions of Ovol as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.
Publication Title
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/2-deficient epidermal cells fail to undertake alpha-catenindriven actin cytoskeletal reorganization and adhesive maturation, and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations as well as defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-a-catenin sequential repression and highlight novel functions of Ovol as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.
Publication Title
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/2-deficient epidermal cells fail to undertake alpha-catenindriven actin cytoskeletal reorganization and adhesive maturation, and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations as well as defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-a-catenin sequential repression and highlight novel functions of Ovol as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.
Publication Title
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/2-deficient epidermal cells fail to undertake alpha-catenindriven actin cytoskeletal reorganization and adhesive maturation, and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations as well as defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-a-catenin sequential repression and highlight novel functions of Ovol as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.
Publication Title
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cyclodextrin protects podocytes in diabetic kidney disease.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C).
Publication Title
Cyclodextrin protects podocytes in diabetic kidney disease.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21. Overall design: eight adult male C57BL6 mice were maintained at thermoneutral temperature (29C). After two weeks, a subset of four mice was placed at 4C environment temperature for 24h. RNAseq was performed on the BAT tissues of these 2 groups.
Publication Title
The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples