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Expression data from isolated terminal end buds in mammary glands with or without Ovol2 deletion

ABSTRACT: 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. TEBs from control and conditional Ovol2-knockout mammary glands were physically isolated for RNA extraction and hybridization on Affymetrix microarrays. In order to identify primary changes, we analyzed TEBs from 24-25-day-old mice, when morphological differences between control and Ovol2 SSKO were still minimal.

ORGANISM(S): Mus musculus

SUBMITTER: Kazuhide Watanabe

PROVIDER: E-GEOD-53923 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2 transcriptional repressor

Project 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. Refer to individual Series

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Expression data from isolated keratinocytes from mouse skin with or without Ovol1 and Ovol2 expression

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Project 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.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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