Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

P53 binding in mouse embryonic stem cells untreated or treated with adriamycin

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE16427 | GEO | 2010/01/19

SECONDARY ACCESSION(S): PRJNA116373

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

p53 regulates the Wnt signaling pathway in murine embryonic stem cells

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

Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts

Project description:Wnt/b-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (PorcnDel/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of PorcnDel organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable, and that stromal production of Wnts can fully support normal murine intestinal homeostasis. Microarray was performed on samples enriched for stromal or epithelial cells from small intestine from Porcn(Del)/Villin-Cre and Porcn(WT)/Villin-Cre male C57Bl/6 mice.

2014-04-19 | E-GEOD-56911 | biostudies-arrayexpress

Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts

2014-04-19 | GSE56911 | GEO

Tbx3 controls Dppa3 levels to regulate exit from pluripotency towards mesodermal lineage

Project description:Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps maintain a naïve pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine-tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state towards mesoderm differentiation. ChIPSeq and RNASeq (population and single cell) was performed on the indicated cell lines. Replicates are indicated as needed. The mm9 genome assembly was used. For single cell mRNA-Seq preparation, SSEA1+DAPI- mESCs were sorted and collected.

2015-07-21 | E-GEOD-60066 | biostudies-arrayexpress

Pyrvinium pamoate targets to multiple vulnerabilities of Merkel cell carcinoma

Project description:Among several WNT signaling perturbagens, we identified pyrvinium pamoate, an FDA-approved anthelminthic drug that exhibits anti-tumor abilities in multiple cancers. Through the integration of transcriptomic, network, and molecular analyses, we discovered that pyrvinium is broadly effective against Merkel cell carcinoma cell lines, and it targets multiple proposed MCC tumorigenesis pathways. Our study revealed that pyrvinium exerts anti-tumor activity in MCC not only through perturbing the canonical and non-canonical WNT signaling pathway but also non-specifically inhibiting cell growth - via the activation of the p53-mediated apoptosis pathway, modulation of mitochondrial function, and induction of endoplasmic reticulum (ER) stress.

2023-11-06 | GSE229701 | GEO

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Project description:We performed bulk RNA sequencing of cells exposed to either 300ng/ml of the ligand WNT3A for 6 or 18 hours, or 8μM of the GSK3b inhibitor CHIR99021 for 6 hours, which is commonly used as a substitute for WNT in differentiation. We observed transcriptional activation of the canonical WNT genes WNT3 and WNT10B confirming that Wnt signaling induces canonical WNTs.

2023-10-10 | GSE245027 | GEO

Tbx3 controls Dppa3 levels to regulate exit from pluripotency towards mesodermal lineage

2015-07-21 | GSE60066 | GEO

Identification of target genes of the transcription factors TCF1 and TCF3 in mouse embryonic stem cells (ChIP-Seq)

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

Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells.

Project description:Wnt/β-catenin signaling regulates both mouse embryonic stem cell (mESC) self-renewal and differentiation. Here we show that the activity of the Wnt/β-catenin signaling pathway safeguards normal DNA methylation of mESCs. Indeed, loss of Wnt activity correlated with loss of DNA methylation, especially at the imprinting control regions (ICRs) in prolonged in vitro mESC cultures. To address the role of Wnt signaling on ICR methylation we performed Reduced Representation Bisulfite Sequencing (RRBS) on both “Young” and “Old” mESCs, being at early and late passages, respectively. We found that several ICRs (both maternal and paternal) showed loss of methylation in “Old” cells that correlates with lower Wnt downstream target expression and lower β-catenin protein level, when compared to “Young” mESCs. In parallel, we analyzed the ICR methylation level also in two Wnt mutant clones after prolonged in vitro culture (O-S33Y #1 and #2). The mutant clones maintained high Wnt activity with passages, similar to “Young” mESCs and ICR methylation level at around 50%, further supporting the beneficial role of Wnt/β-catenin pathway on mESC epigenetic stability and homeostasis.

2019-02-07 | GSE109417 | GEO

Transcription profiling by array of human p73 over-expressing H1299 cells

Project description:The integral role of p53 in tumor suppression has promted many laboratories to perform extensive analyses of signaling pathways downstream of the p53 family of sequence-specific DNA binding transcription factors (p53 and its homologs p63 and p73). Despite the ability of p73 to regulate many p53 family target genes, little is known about the specific pathways that modulate p73 during development, tumorigenesis and tumor therapy. In this study we present a gene signature-based approach for connecting signaling pathways to transcription factors, as exemplified by p73. We generated a p73 gene signature by integrating whole-genome chromatin immunoprecipitation and expression profiling. Experiment Overall Design: H1299 lung carcinoma cells were infected with p73 expressing or control adenovirus for 5 h and then harvested.

2008-10-20 | E-GEOD-11626 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data