Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116375 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide analysis of gene expression changes in murine embryonic stem cells (R1E cells) treated with Ultraviolet and adriamycin Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development.
2010-01-19 | GSE16428 | GEO
Project description:Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development
2010-01-19 | GSE16427 | GEO
Project description:In colorectal cancer, p53 is commonly inactivated, associated with chemo-resistance, and marks the transition from non-invasive to invasive disease. Cancers, including colorectal cancer, are thought to be diseases of aberrant stem cell populations, as stem cells are able to self-renew, making them long-lived enough to acquire mutations necessary to manifest the disease. We have shown that extracts from sweet sorghum stalk components eliminate colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms are unknown. In the present study, CCSC were transfected with short hairpin-RNA against p53 (CCSC p53 shRNA) and treated with sweet sorghum phenolics extracted from different plant components (dermal layer, leaf, seed head and whole plant). While all components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspases 3/7 activity, PARP cleavage, and DNA fragmentation in a p53-dependent and p53-independent fashion, respectively. Further investigations revealed that the anti-proliferative and pro-apoptotic effects were associated with decreases in beta-catenin protein levels, and beta-catenin targets cyclin D1, cMyc, and survivin. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against human colon cancer stem cells are via suppression of Wnt/beta-catenin pro-survival signaling in a p53-dependent (dermal layer) and partial p53-independent (seed head) fashion. LCMS used to identify phenolic compounds associated with extract activity
2014-05-01 | MTBLS69 | MetaboLights
Project description:Wnt/-catenin signaling controls self-renewal and pluripotency maintenance in both embryonic and adult stem cells (SCs) in mouse. We show that the activation of Wnt pathway drastically reduces proliferation of mESCs by direct binding of the the Wnt-effector Tcf1 to directly binds and regulates the Ink4/Arf locus , thereby Wnt pathway activation drastically reduces proliferation of mESCs and its regulation. We have conducted ChipSeq experiments for Tcf1 and Tcf3 with background to identify the genome wide binding locations Tcf1 and Tcf3 in mouse ESC.
2017-03-14 | E-MTAB-4358 | biostudies-arrayexpress
Project description:Wnt/b-catenin signaling regulates sequential fate decisions of murine cortical precursor cells
| PRJNA287701 | ENA
Project description:The objective of this study was to identify genes regulated by canonical Wnt signaling in mouse embryonic stem cells (ESCs).Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and ?-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and ?-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by ?-catenin entry into this complex. Wnt pathway stimulation also triggers ?-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to promote mouse ESC differentiation. Triplicates of mouse embryonic stem cells cultured with GSK3 inhibitor CHIR99021 or with Wnt pathway inhibitor XAV939.
2013-03-01 | E-GEOD-43420 | biostudies-arrayexpress
Project description:Both FGF and WNT pathways play important roles in embryonic development, stem cell self-renewal and are frequently deregulated in breast cancer. To study the cooperation between FGF and WNT signaling, we have generated a mouse model, MMTV-WNT1/MMTV-iFGFR1 (WNT/iR1), in which we could chemically overactivate iFGFR1 in a ligand-independent manner.
2017-11-22 | MSV000081730 | MassIVE
Project description:Wildtype murine embryonic stem cells were kept undifferentiated or treated with retinoic acid for 4 days. We used SABioscience p53 Signaling Pathway Array to quantitate gene expression of genes involved in survival and cell death from the immature and the differently activated cells.
2015-10-16 | GSE74086 | GEO
Project description:Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven-nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK-extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. The transcription elongation factor Ell3 induces chemosensitization of MCF7 cells to the chemotherapeutic agent cis-diamminedichloroplatinum (II) (CDDP) by stabilizing p53. Interestingly, Ell3 induced p53 stabilization in response to CDDP by promoting binding of p53 to NADH quinoneoxidoreductase 1 (NQO1), which is linked to an ubiquitin-independent degradation pathway, as well as by suppressing a MDM2 mediated ubiquitin-dependent degradation pathway. Furthermore, Ell3 enhanced interleukin-20 (IL-20) expression leading to the activation of the ERK1/2 signaling pathway. By analyzing the suppressive effects of IL-20 and ERK signaling in the Ell3 expressing MCF7 cells, we confirmed that the IL-20 mediated ERK1/2 signaling pathway is the main cause of p53 stabilization after CDDP exposure in MCF7 cells. Ell3-overexpressing breast cancer cell lines were established using the chromosomal integration of an Ell3 expression plasmid, which was constructed by cloning PCR-amplified Ell3 cDNA into pcDNA3.1 vectors (Invitrogen, Carlsbad, CA; https://www.lifetechnologies.com). Three independent Ell3 overexpressing cell lines were generated. The gene expression profiles of wild type MCF7 and Ell3 overexpressing cell line were compared using Affymetrix PrimeView arrays.
2015-11-25 | E-GEOD-63612 | biostudies-arrayexpress
Project description:PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and glioma
| PRJNA126665 | ENA