ZEB2, a master regulator of the epithelial-mesenchymal transition, mediates trophoblast differentiation
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PROVIDER: PRJNA478940 | ENA |
REPOSITORIES: ENA
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Project description:Comparison of genes associated with the EMT between trophoblast cell line (BeWo, JEG3) controls and cells overexpressing the ZEB2 gene (BeWo ZEB2oe, JEG_ZEB2oe).
2018-10-01 | GSE116532 | GEO
Project description: Not available
| S-EPMC6497037 | biostudies-literature
Project description:infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
2021-03-23 | PXD022212 | Pride
Project description:Study of loss of ZEB2 in breast cancer cells in vitro and in vivo: gene expression and phenotypic switch to more benign behavior of the cancer cells. Morphological, functional and gene microarray analysis following ZEB2 knockdown in MDAMB231 cells reveals gain of epithelial differentiation, reduction of migration, invasion and metastatic capability. The measurement of ZEB2 transcriptional activity in tumor cells efficiently predicts the probability of breast cancer patient survival. Global gene expression profiles were measured using Affymetrix U133 plus2 microarrays in MDAMB231 cells (control and ZEB2 shRNA and siRNA knockdown cells on plastic)
2016-03-15 | E-GEOD-27966 | biostudies-arrayexpress
Project description:The multi-domain transcription factor ZEB2 controls embryonic and adult cell fate decisions and maturation in many stem/progenitor cell types. Defects in these processes in specific cell types underlie Mowat-Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of an approximately 3.5 Mb-long gene-desert, lacking any protein-coding gene sequence. Using temporal high-resolution Targeted Chromatin Capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 gene promoter and this gene desert during neural differentiation of induced pluripotent cells (iPSCs), including at early neuroprogenitor cell (NPC)/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500 kb upstream of the ZEB2 transcription start site (TSS). Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis regulatory elements (REs) located in ZEB2’s gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of relevant cell types, and the molecular characterization of identified MOWS patients that lack mutations in ZEB2 protein-coding exons.
2020-08-03 | GSE147000 | GEO
Project description:T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during infection. We find that at high concentrations T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing (ChIP-seq) showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential. Splenocyte derived CD8+ T cells from C57BL/6 mice with either a wildtype (WT) (GzmB-Cre Zeb2+/+) or GzmB-Cre Zeb2-fl/fl (Zeb2-/-) backgrounds, following 8 days post infection with LCMV-Armstrong, were subsetted into KLRG1-hi/IL-7R-lo populations (terminal effectors, TE) or KLRG1-lo/IL-7R-hi (memory precursors, MP) populations. Four experimental groups, each with 3 samples, comprised of TE+WT, MP+WT, TE+ZEB2-/-, and MP+ZEB2-/-, were profiled for gene expression utilizing a polyA RNA prep and hybridized to the Illumina microarray platform IlluminaWG-v2.0.
2015-09-15 | E-GEOD-72408 | biostudies-arrayexpress
Project description:To elucidate the direct targets of ZEB2 in ABCs, we performed high-throughput sequencing of regulome by ATAC-seq, CUT & Tag, and CUT & RUN, leading to the identification the accessible sites with ZEB2 binding. Among the genes differentially expressed by Zeb2 deficiency, we found 33 candidate target genes of ZEB2, with 22 repressed and 11 activated by ZEB2. The critical transcription factor Mef2b, essential for GC development, was repressed by ZEB2. This direct regulation was mapped to a conserved region about 20kb downstream of Mef2b's exon I TSS, enriched with enhancer-associated features in both human and mouse.
2023-12-31 | GSE242607 | GEO
Project description:The transformation of cytotrophoblast (CTB) to extravillous trophoblast (EVT) is an essential process for placental implantation. EVT generated at the tips of the anchoring villi migrate away from the placenta and invade the endometrium and maternal spiral arteries, where they modulate maternal immune responses and remodel the arteries into high-volume conduits to facilitate uteroplacental blood flow. The process of EVT differentiation has several factors in common with the epithelial-to-mesenchymal transition (EMT) observed in embryonic development, wound healing and cancer metastasis. We hypothesized that the generation of invasive EVT from CTB was a form of EMT. We isolated paired CTB and EVT from first trimester placentae by flow cytometry for integrin beta 4 (CTB) and HLA-G (EVT). We compared their gene expression using a PCR array comprising probes for genes involved in EMT. Out of 84 genes, 24 were down-regulated in EVT compared to CTB, including epithelial markers such as E-cadherin (-11-fold) and occludin (-75-fold). Another 30 genes were up-regulated in EVT compared to CTB including mesenchymal markers such as vimentin (235-fold) and fibronectin (107-fold) as well as the matrix metalloproteinases, MMP2 and MMP9 (357-fold, 129-fold). These alterations also included major increases in the ZEB2 (zinc finger E-box binding homeobox 2, 198-fold) and TCF4 (transcription factor 4, 18-fold) transcription factors, recognized as EMT master regulators, suggesting possible stimulatory mechanisms. There was substantial up-regulation of the genes encoding TGFb1 and TGFb2 (48-fold, 115-fold), which may contribute to the maintenance of the mesenchymal-like phenotype. We conclude that transformation of CTB to EVT is consistent with an EMT, although the differences with other types of EMT suggest this may be a unique form
2015-10-15 | GSE74040 | GEO
Project description:Expression data from WT cDC1s, Zeb2 KO cDC1s, Nfil3 Zeb2 DKO cDC1s and Zeb2 Id2 DKO cDC1s
| PRJNA509887 | ENA
Project description:Age-associated B cells (ABCs) accumulate during infection, aging and autoimmunity, contributing to lupus pathogenesis. Here, we screened for transcription factors driving ABC formation and found Zeb2 was required for human and mouse ABC differentiation in-vitro. ABCs were reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with TLR7-driven lupus, Zeb2 was essential for ABC formation and autoimmune pathology. Zeb2 binds to the +20kb intronic enhancer of Mef2b, repressing Mef2b-mediated germinal center B cell differentiation and promoting ABC formation. Zeb2 also targets genes important for ABC specification and function including Itgax. Zeb2-driven ABC differentiation required Jak-Stat signaling, and treatment with the Jak1/3 inhibitor tofacitinib reduced ABC accumulation in mice and autoimmune patients. Zeb2 thus emerges as a driver of B-cell autoimmunity.
2023-12-31 | GSE242611 | GEO