Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intestinal region-specific Wnt signalling profiles reveal interrelation between cell identity and oncogenic pathway activity in cancer development

ABSTRACT: We use a 3D in vitro organoid model to study the early phase of colorectal cancer development. In reaction to Wnt activation we observe downregulation of location specific genes and differentiation markers. Furthermore, the signature of Wnt target genes differs between organoids representing three locations of the murine intestine. The location specific Wnt signatures are dominated by genes which have been lowly expressed in the tissue of origin, and are the targets of transcription factors that are activated following enhanced Wnt signalling. We concude that the cell of origin has a substantial effect on the reaction to Wnt activation in a simple intestinal adenoma model.

ORGANISM(S): Mus musculus

PROVIDER: GSE146476 | GEO | 2020/12/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes

Project description:Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GHsecreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMC gene in ACTH secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes.

2020-03-26 | GSE147548 | GEO

Human colon organoids reveal distinct physiologic and oncogenic Wnt responses

Project description:Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC.

2019-02-28 | PXD012650 | Pride

Concomitant Loss of Smad4 and Activation of Wnt Signaling Triggers Enterocyte De-differentiation and Adenoma Formation

Project description:In the current work, we add to the understanding of differentiated-cell-derived tumorigenesis by demonstrating that simultaneous loss of SMAD4 and activation of the WNT pathway triggers stem cell properties and adenoma formation in the differentiated epithelium. Under normal conditions, SMAD4 loss does not immediately affect the normal tissue homeostasis in the intestine. However, after approximately 6 months, adenomas will develop and feature elevated WNT signaling, suggesting that SMAD4 loss predisposes to WNT-driven tumors. Interestingly, ectopic elevation of WNT in the context of a SMAD4 mutant background triggers stem cell activity and adenoma formation in the differentiated epithelium. Thus Smad4 functions to suppress villus cells from re-entering the cell cycle and functioning as stem cells upon exposure to high levels of WNT. Thus, we report a new mechanism through which differentiated cells can contribute to tumor formation.

2018-07-23 | GSE102171 | GEO

Telomeric Chromosomal Instability Fosters Paracrine Mediated Cell Competition to Initiate Intestinal Cancer [bulk RNA-seq]

Project description:Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer- relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased the rate of neoplastic cell clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apcmin mice. Mechanistically, CIN represses EZH2 leading to upregulation of secreted Wnt antagonists, which resulted in a growth advantage to CIN-high neoplastic cells. Correspondingly, pharmacological activation of intrinsic WNT signaling enhanced intestinal stem cells fitness, leading to reduced neoplastic cell clonal expansion and adenoma burden. Thus, the CIN-EZH2-WNT axis enhances intestinal cancer initiation in the nascent tumor microenvironment, providing a preventive strategy for patients harboring germline APC mutations.

2024-03-01 | GSE234032 | GEO

Telomeric Chromosomal Instability Fosters Paracrine Mediated Cell Competition to Initiate Intestinal Cancer [scRNA-seq]

2024-03-01 | GSE234031 | GEO

Telomeric Chromosomal Instability Fosters Paracrine Mediated Cell Competition to Initiate Intestinal Cancer [CUT&RUN]

2024-03-01 | GSE234030 | GEO

Telomeric Chromosomal Instability Fosters Paracrine Mediated Cell Competition to Initiate Intestinal Cancer (WGS)

2024-03-05 | GSE229828 | GEO

High-resolution genome replication profiles, modeling and single-cell imaging define the stochastic nature of replication initiation and termination

Project description:Eukaryotic genome replication is stochastic with each cell using a different cohort of replication origins. Interpreting high-resolution genome replication profiles with a mathematical model allowed us to quantify the stochastic nature of genome replication. This approach included estimation of the activity of every replication origin and the genome-wide location of replication termination events. Single-cell measurements verified the inferred values for stochastic origin replication time. Strains in which multiple origins had been inactivated, confirmed that the location of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci. Measurement of genome replication time for two S. cerevisiae strains. For each strain six S phase samples werecompared with a non-replicating sample.

2013-11-07 | E-GEOD-48561 | biostudies-arrayexpress

Analyzing the effect of Lef1 deletion in mouse intestinal adenoma cells with single-cell RNA sequencing

Project description:Somatic mutations in APC or CTNNB1 genes lead to aberrant Wnt signaling and colorectal cancer (CRC) initiation and progression. Activation of Wnt pathway leads to the formation of beta-catenin-T-cell factor/Lymphoid enhancer binding factor 1 (Tcf/Lef1) complexes that activate transcription of oncogenic target genes. Lef1 is the only member of the Tcf gene family that is not expressed in the normal intestine, but is induced during intestinal tumorigenesis. Thus, we wanted to assess the role of Lef1 using genetic mouse models of intestinal adenomas and scRNA-seq technology. Tumorigenesis was initiated by inducing Apc mutation in Lgr5+ stem cells. Intestinal EpCAM+ epithelial cells of Lgr5-CreERT;Apc fl/fl (LApc) mouse and Lgr5-CreERT;Apc fl/fl; Lef1 fl/fl (LApcL) mouse were used to analyze the effects of Lef1 deletion in intestinal adenoma cells. We used WT mice as a control to distinguish adenoma cells.

2021-12-10 | GSE179483 | GEO

The transcription factor GATA6 allows self-renewal of colon adenoma stem cells by repressing BMP gene expression.

Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 represses BMP4 gene expression through binding to a regulatory region that has been previously linked to increased susceptibility to develop CRC. Thus, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation. Total RNA from biological replicates of VillinCreERT2Gata6+/+Apcfl/fl and VillinCreERT2Gata6fl/flApcfl/fl colon adenoma tumor organoids grown for one week in control media (see growth protocol).Total RNA was extracted using the TRIzolM-BM-. Plus RNA Purification Kit (Life Technologies).

2014-06-19 | E-GEOD-49479 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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