Similar Datasets
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). 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. We report ChIPseq data illustrating Ovol2 genome-wide targets in mouse mammary epithelial cells, suggesting that Ovol2 regulates a plethora of genes associated with the EMT process. Immunoprecipitated samples from HC11 mouse mammary epithelial cells with antibodies against Ovol2 and control IgG respectively were used for ChIP-seq experiments.
2014-03-19 | E-GEOD-53925 | biostudies-arrayexpress
Project description:The placenta establishes the interface between maternal and fetal tissues during pregnancy, enabling the selective exchange of nutrients and gases between maternal and fetal circulations. In humans and mice, this exchange surface is lined by a multinucleated epithelial layer called the syncytiotrophoblast (SynT). SynT formation from trophoblast precursors requires epithelial plasticity to permit cell differentiation, fusion, and morphogenesis, while preserving epithelial integrity to maintain the maternal-fetal exchange barrier. However, the mechanisms that safeguard epithelial features during SynT development remain unclear. OVO-like 2 (OVOL2), a transcriptional repressor of mesenchymal programs and key regulator of epithelial identity, is highly expressed in the mouse placenta and essential for its development. We hypothesized that OVOL2 promotes SynT lineage formation by restricting mesenchymal transformation during trophoblast differentiation. To test this, placental development was examined following Ovol2+/- matings, and wild-type and Ovol2-deficient trophoblast stem cells were analyzed under stem conditions or differentiated with CHIR99021 to enrich for SynT lineages. SynT lineage development was disrupted in both Ovol2-deficient placentas and differentiating trophoblast stem cells. Chromatin profiling identified OVOL2 binding near genes associated with epithelial-to-mesenchymal transition, including Id1, Zeb1, and Vim, which were upregulated in Ovol2-deficient trophoblasts. Consistent with these observations, Ovol2-deficient cells showed elevated levels of mesenchymal markers such as ZEB1 and Vimentin and reduced levels of epithelial markers including E-cadherin. These findings identify OVOL2 as a critical regulator of SynT lineage formation and epithelial identity in the mouse placenta.
2026-08-31 | GSE324788 | GEO
Project description:The placenta establishes the interface between maternal and fetal tissues during pregnancy, enabling the selective exchange of nutrients and gases between maternal and fetal circulations. In humans and mice, this exchange surface is lined by a multinucleated epithelial layer called the syncytiotrophoblast (SynT). SynT formation from trophoblast precursors requires epithelial plasticity to permit cell differentiation, fusion, and morphogenesis, while preserving epithelial integrity to maintain the maternal-fetal exchange barrier. However, the mechanisms that safeguard epithelial features during SynT development remain unclear. OVO-like 2 (OVOL2), a transcriptional repressor of mesenchymal programs and key regulator of epithelial identity, is highly expressed in the mouse placenta and essential for its development. We hypothesized that OVOL2 promotes SynT lineage formation by restricting mesenchymal transformation during trophoblast differentiation. To test this, placental development was examined following Ovol2+/- matings, and wild-type and Ovol2-deficient trophoblast stem cells were analyzed under stem conditions or differentiated with CHIR99021 to enrich for SynT lineages. SynT lineage development was disrupted in both Ovol2-deficient placentas and differentiating trophoblast stem cells. Chromatin profiling identified OVOL2 binding near genes associated with epithelial-to-mesenchymal transition, including Id1, Zeb1, and Vim, which were upregulated in Ovol2-deficient trophoblasts. Consistent with these observations, Ovol2-deficient cells showed elevated levels of mesenchymal markers such as ZEB1 and Vimentin and reduced levels of epithelial markers including E-cadherin. These findings identify OVOL2 as a critical regulator of SynT lineage formation and epithelial identity in the mouse placenta.
2026-08-31 | GSE324789 | GEO
Project description:In this assay OVOL2 was overexpressed in 3 MOS PDA cell lines to investigate its ability to reprogram cells toward the GLS subtype.
2026-01-16 | GSE280160 | GEO
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). 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. We report ChIPseq data illustrating Ovol2 genome-wide targets in mouse mammary epithelial cells, suggesting that Ovol2 regulates a plethora of genes associated with the EMT process.
2014-03-19 | GSE53925 | GEO
Project description:The mRNA expression profile was performed to study the downstream genes regulated by TET2 in human breast cancer cells. In MCF7 cells, CRISPR method was used to knock out TET2 and shRNA was used for knocking down TET2. Through the deep sequencing and analysis of wild-type and loss of TET2 MCF7 cells, we identified the negative regulation of PD-L1 gene transcription by TET2.
2021-06-01 | GSE164032 | GEO
Project description:Ripk3-deficient fibroblasts and lung epithelial cells are resistant to influenza-induced cell deaths. However, Ripk3 is required for protection against influenza infection in vivo. Here, we examine the influenza-regulated gene expressions between wild type and knock out MEFs as well as an involvement of kinase activity if any.
2016-10-14 | GSE80740 | GEO
Project description:In development, embryonic ectoderm differentiates into several lineages including neuroectoderm and surface ectoderm, through the mechanism largely unclear. Here we report that OVOL2 is required for the transcriptional program of corneal epithelium cell(CEC)s, a derivative of surface ectoderm, and it might regulates the differential transcriptional programs between the two lineages. By a functional screening, we identified transcription factors (TFs) maintaining human CECs. OVOL2 was necessary to maintain the transcriptional program in CECs, particularly through repressing expression of mesenchymal genes. OVOL2 combined with several TFs were able to activate the transcriptional program of CECs in fibroblasts, accompanied by induction of chromatin landscape. Moreover, our analysis revealed that neuroectoderm derivatives express some of mesenchymal genes. In fact, OVOL2 alone was able to induce the transcriptional program of CECs in neural progenitor cells (NPCs) through repression of mesenchymal genes as well as activation of epithelial genes. Our data suggest that the difference between the transcriptional programs of surface ectoderm-derivatives and neuroectoderm-derivatives is regulated in part by the reciprocally-repressive mechanism between epithelial and mesenchymal genes that is seen in epithelial-to-mesenchymal transition.
2016-04-11 | GSE79251 | GEO
Project description:In development, embryonic ectoderm differentiates into several lineages including neuroectoderm and surface ectoderm, through the mechanism largely unclear. Here we report that OVOL2 is required for the transcriptional program of corneal epithelium cell(CEC)s, a derivative of surface ectoderm, and it might regulates the differential transcriptional programs between the two lineages. By a functional screening, we identified transcription factors (TFs) maintaining human CECs. OVOL2 was necessary to maintain the transcriptional program in CECs, particularly through repressing expression of mesenchymal genes. OVOL2 combined with several TFs were able to activate the transcriptional program of CECs in fibroblasts, accompanied by induction of chromatin landscape. Moreover, our analysis revealed that neuroectoderm derivatives express some of mesenchymal genes. In fact, OVOL2 alone was able to induce the transcriptional program of CECs in neural progenitor cells (NPCs) through repression of mesenchymal genes as well as activation of epithelial genes. Our data suggest that the difference between the transcriptional programs of surface ectoderm-derivatives and neuroectoderm-derivatives is regulated in part by the reciprocally-repressive mechanism between epithelial and mesenchymal genes that is seen in epithelial-to-mesenchymal transition.
2016-04-11 | GSE67821 | GEO
Project description:We report the transcriptional difference of LATS1/2 gene knock out T47D cells with wild type control using RNA-seq technology. We further generated the chromatin binding of multiple proteins, including YAP, TEAD2, Estrogen receptor alpha, VGLL3 and several histone marks, as well as ATAC profiling between LATS1/2 gene knock out MCF7 cells with wild type control.
2022-01-11 | GSE181460 | GEO