Enhancement of direct reprogramming from fibroblasts to epithelial lineages by OVOL2-induced mesenchymal-to-epithelial transition [CAGE]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA503198 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8142330.fastq.gz | Fastqsanger.gz | |||
| SRR8142331.fastq.gz | Fastqsanger.gz | |||
| SRR8142332.fastq.gz | Fastqsanger.gz | |||
| SRR8142333.fastq.gz | Fastqsanger.gz | |||
| SRR8142334.fastq.gz | Fastqsanger.gz |
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Project description:Mesenchymal-to-epithelial transition (MET) is an important step in cell reprogramming from fibroblast, a most frequently used cell type for this purpose, to various epithelial cell types. However, how MET can be induced in fibroblast has not been fully studied. In this study, we sought for transcription factors (TFs) that can efficiently induce MET in dermal fibroblasts and identified OVOL2 as a potent inducer of key epithelial genes. In addition, OVOL2 cooperatively enhanced MET induced by HNF1A, TP63 and KLF4, known reprogramming TFs to epithelial lineages. In TP63/KLF4-induced fibroblast-keratinocyte cell reprogramming, OVOL2 greatly facilitated activation of epithelial genes as well as keratinocyte-specific genes. This enhancement of epithelial gene expression program was accompanied by enhanced changes in chromatin accessibility across the genome. Mechanistically, motif enrichment analysis revealed that target loci of KLF4 and TP63 become accessible upon reprogramming while OVOL2 target loci become inaccessible, indicating that KLF4 and TP63 positively regulate their targets while OVOL2 primarily induces closed chromatin state at its target loci. Thus, OVOL2 and tissue-specific reprogramming factors cooperatively facilitate cell reprogramming of fibroblast into epithelial lineages through distinct mechanisms.
2019-05-17 | GSE122034 | GEO
Project description:Mesenchymal-to-epithelial transition (MET) is an important step in cell reprogramming from fibroblast, a most frequently used cell type for this purpose, to various epithelial cell types. However, how MET can be induced in fibroblast has not been fully studied. In this study, we sought for transcription factors (TFs) that can efficiently induce MET in dermal fibroblasts and identified OVOL2 as a potent inducer of key epithelial genes. In addition, OVOL2 cooperatively enhanced MET induced by HNF1A, TP63 and KLF4, known reprogramming TFs to epithelial lineages. In TP63/KLF4-induced fibroblast-keratinocyte cell reprogramming, OVOL2 greatly facilitated activation of epithelial genes as well as keratinocyte-specific genes. This enhancement of epithelial gene expression program was accompanied by enhanced changes in chromatin accessibility across the genome. Mechanistically, motif enrichment analysis revealed that target loci of KLF4 and TP63 become accessible upon reprogramming while OVOL2 target loci become inaccessible, indicating that KLF4 and TP63 positively regulate their targets while OVOL2 primarily induces closed chromatin state at its target loci. Thus, OVOL2 and tissue-specific reprogramming factors cooperatively facilitate cell reprogramming of fibroblast into epithelial lineages through distinct mechanisms.
2019-05-17 | GSE122035 | GEO
Project description:Enhancement of direct reprogramming from fibroblasts to epithelial lineages by OVOL2-induced mesenchymal-to-epithelial transition
| PRJNA503197 | ENA
Project description:Enhancement of direct reprogramming from fibroblasts to epithelial lineages by OVOL2-induced mesenchymal-to-epithelial transition [ATAC-seq]
| PRJNA503199 | ENA
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:Thymic epithelial cells (TECs) begin to develop embryonically in mice and humans, expand in number through puberty, and then stabilize before declining during early adulthood. We identified a mechanism by which TEC numbers and function are maintained postnatally, discovered through a forward genetic screen for altered immune cell development in mice. A viable missense allele (C120Y) of Ovol2 resulted in lymphopenia, in which T cell development was compromised by loss of medullary TECs and dysfunction of cortical TECs. OVOL2 is an essential regulator of epithelial to mesenchymal transition (EMT), and we show that the epithelial identity of TECs is subverted towards a mesenchymal state in OVOL2-deficient mice. We document global changes in chromatin accessibility correlated with gene expression, particularly affecting genes involved in epithelial and mesenchymal cell proliferation and differentiation. OVOL2 regulates chromatin accessibility by inhibiting the BRAF-HDAC complex. In particular, it disrupts the RCOR1-LSD1 complex by directly binding to the lysine demethylase LSD1, resulting in inhibition of LSD1-mediated H3K4me2 demethylation. Thus, OVOL2 controls the epigenetic landscape of TECs, preventing EMT and enforcing TEC identity to support T cell development in the thymus.
2022-12-21 | MSV000090946 | MassIVE
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:This paper shows, for the first time, a novel function of the OVO-like proteins (OVOL1and OVOL2) as critical inducers of mesenchymal to epithelial transition (MET) in human cancer. Examination of the effects of OVOL1 and OVOL2 overexpression in a prostate cancer model.
2013-08-01 | E-GEOD-48230 | biostudies-arrayexpress
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