Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174133 | ENA |
REPOSITORIES: ENA
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Project description:Endothelial to mesenchymal transition (EndoMT) plays a key role in heart development, but is also implicated in cardiovascular diseases in postnatal life. While the roles of TGF-β as inducer of EndoMT on the transcriptional level are well characterised, its post-transcriptional regulatory mechanisms remain largely unknown. Here, we identified global changes in the endothelial mRNA bound proteome upon TGF-β stimulation using RNA interactome capture. Characterisation of TGF-β regulated RNA binding proteins (RBPs) revealed heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and Cold Shock Domain Containing E1 (Csde1) as key regulators of endothelial function and EndoMT. We profiled TGF-β driven changes in the RNA binding patterns of hnRNP H1 and Csde1 and found that they dynamically bind and regulate specific subsets of functionally connected RNAs related to mesenchymal activation upon TGF-β stimulation. Together, we show that RBPs play a key role in EndoMT and that the RBPs hnRNP H1 and Csde1 maintain endothelial cell function and counteract mesenchymal activation.
2023-10-01 | GSE216227 | GEO
Project description:Endothelial to mesenchymal transition (EndoMT) plays a key role in heart development, but is also implicated in cardiovascular diseases in postnatal life. While the roles of TGF-β as inducer of EndoMT on the transcriptional level are well characterised, its post-transcriptional regulatory mechanisms remain largely unknown. Here, we identified global changes in the endothelial mRNA bound proteome upon TGF-β stimulation using RNA interactome capture. Characterisation of TGF-β regulated RNA binding proteins (RBPs) revealed heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and Cold Shock Domain Containing E1 (Csde1) as key regulators of endothelial function and EndoMT. We profiled TGF-β driven changes in the RNA binding patterns of hnRNP H1 and Csde1 and found that they dynamically bind and regulate specific subsets of functionally connected RNAs related to mesenchymal activation upon TGF-β stimulation. Together, we show that RBPs play a key role in EndoMT and that the RBPs hnRNP H1 and Csde1 maintain endothelial cell function and counteract mesenchymal activation.
2023-10-01 | GSE216226 | GEO
Project description:Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3M-bM-^@M-^Y-UTR regulatory BAT (TGFM-NM-2 activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3M-bM-^@M-^Y-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts. We adopted a combinatorial approach involving polysome profiling and RIP-Chip analyses using hnRNP E1 and filtered the array data based on the regulatory mechanism of Dab2 and ILEI. This led to the identification and validation of a cohort of target mRNAs that follow the same pattern of regulation as Dab2 and ILEI. To identify potential target mRNA transcripts that are translationally regulated by hnRNP E1 in a TGF-beta-dependent manner, we adopted a combinatorial approach involving expression profiling analyses and RNA immunoprecipitation analysis (RIP-Chip). We performed a screen using: 1) total mRNA and 2) RNA isolated from monosomal (non-translating) versus polysomal (translating) fractions from TGF-beta-treated (24 h) and non-treated NMuMG cells and from the hnRNP E1 knockdown derivative (E1KD), that undergo constitutive EMT even in the absence of TGF-beta. In addition, we screened for transcripts that selectively interact with hnRNP E1 in NMuMG cells under unstimulated conditions and subsequently lose their temporal association following TGF-beta stimulation. The samples were individually hybridized to Affymetrix GeneChipM-BM-. Mouse Genome 430 2.0 arrays.
2012-08-30 | E-GEOD-40466 | biostudies-arrayexpress
Project description:TGF-beta is one of the most important cytokines that induce epithelial to mesenchymal transition (EMT). In this dataset, we examined TGF-beta induced changes in gene and exon level expression. Core probesets of two samples were analyzed. NMuMG cells were stimulated with TGF-beta for 24 h or left untreated.
2011-11-01 | E-GEOD-28184 | biostudies-arrayexpress
Project description:Transforming growth factor-beta (TGF-beta) transmits signals that facilitate cancer progression. Especially, epithelial-mesenchymal transition (EMT) induced by TGF-beta is considered to crucially contribute to the malignant phenotype of cancer cells. Here we report that the EMT-associated cellular responses induced by TGF-beta are mediated through distinct signaling pathways that diverge at Smad3; cell motility and epithelial marker downregulation are Smad3-dependent while mesenchymal marker induction is not. Furthermore, using a chimeric protein approach in SMAD3 knockout A549 cells, we found that the beta 4 region in the MH1 domain of Smad3 is indispensable for TGF-beta–induced cell motility, but not for epithelial marker downregulation. A transcriptome analysis was performed using A549 cells expressing Smad3 mutant of the MH1 domain.
2021-03-10 | GSE152015 | GEO
Project description:In this project we evaluated the proteomic profiling with TGF-β stimuli at 24h in a CRISPR-Cas9 model for ALMS1 gene in hTERT-BJ-5ta cells. Proteomic results showed a majority inhibition of downstream regulated pathways by the TGF-β, associating the protein coding genes (PCG) with processes like TGF- β matrix regulation, epithelial mesenchymal transition (EMT), PI3K/AKT or P53. In conclusion, seems that the depletion of ALMS1 could be inhibiting the signals transduction through the TGF -β and the routes regulated downstream.
2024-01-26 | PXD035708 | Pride
Project description:TGF-beta is one of the most important cytokines that induce epithelial to mesenchymal transition (EMT). In this dataset, we examined TGF-beta induced changes in gene and exon level expression.
2011-11-01 | GSE28184 | GEO
Project description:Whole genome bisulfite sequencing of MDCK cells, before and after TGFB-induced epithelial-mesenchymal transition Sequencing of bisulfite converted DNA from MDCK cells untreated, and after a 30 days treatment with TGF beta
2014-08-14 | E-GEOD-43697 | biostudies-arrayexpress
Project description:Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF-β-dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT. Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines. Functionally, GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF-β receptor antagonist, BMP2. The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis. These results indicate that GRHL2 is a suppressor of the oncogenic EMT. 3 biologic replicates for each cell line. Comparison of HMLE+Twist-ER cells expressing GRHL2/pMIG vs. HMLE+Twist-ER cells expressing empty pMIG.
2012-02-25 | E-GEOD-36081 | biostudies-arrayexpress
Project description:The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing.
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