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LGR5 positivity defines stem-like cells in colorectal cancer [aCGH]

ABSTRACT: Lgr5-EGFP-IRES-Cre-ERT2 mice were exposed to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5. To exclude that transcriptional differences between Lgr5 high and low mouse colon tumor cells were imposed by distinct patterns of chromosomal aberrations in the two cell fractions, we also performed array comparative genomic hybridization (aCGH) from these tumors. All eight analyzed tumors were chromosomally stable, and thus, no difference between Lgr5 high and low cells could be detected.

ORGANISM(S): Mus musculus

PROVIDER: GSE46711 | GEO | 2013/05/07

SECONDARY ACCESSION(S): PRJNA202103

REPOSITORIES: GEO

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LGR5 positivity defines stem-like cells in colorectal cancer [aCGH]

Project description:Lgr5-EGFP-IRES-Cre-ERT2 mice were exposed to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5. To exclude that transcriptional differences between Lgr5 high and low mouse colon tumor cells were imposed by distinct patterns of chromosomal aberrations in the two cell fractions, we also performed array comparative genomic hybridization (aCGH) from these tumors. All eight analyzed tumors were chromosomally stable, and thus, no difference between Lgr5 high and low cells could be detected. AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before aCGH was performed. Biological replicates: 8. Two CGH array platforms.

2013-05-07 | E-GEOD-46711 | biostudies-arrayexpress

LGR5 positivity defines stem-like cells in colorectal cancer

Project description:To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. In the AOM/DSS-induced mouse colon tumors Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon epithelial cells. To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we transduced SW480 CRC cells with lentiviral shRNA constructs to silence LGR5 expression. This resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells. Notch signaling was down-regulated upon LGR5 silencing. This was confirmed by immunohistochemistry against cleaved NOTCH1. Normal mouse colons and AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before gene expression was measured. Fifteen independent experiments were performed using seven individual mice for normal colons and eight for tumors. Appropriate LGR5 status was confirmed by real-time qRT-PCR before measuring silencing induced gene expression. Three independent experiments were performed for each cell fraction using separately cultured cells for each experiment.

2013-04-19 | E-GEOD-46200 | biostudies-arrayexpress

LGR5 positivity defines stem-like cells in colorectal cancer [Expression]

2013-04-19 | GSE46200 | GEO

Gene expression data from mouse colon. AOM+DSS induced colitis. Wild type or Cygb -/- mice

Project description:Cytoglobin is a member of the hemoglobin family and is thought to protect against cellular hypoxia and cellular oxidative stress. This function may be particularly important in inflammation induced cancer observed in e.g. patients with ulcerative colitis. In this study, we investigated the development of inflammation and tumors in the murine model of inflammation induced colorectal cancer using Azoxymethane treatment combined with Dextrane Sodium Sulphate.

2017-06-30 | GSE86299 | GEO

Mus musculus breed:FvB

Project description:Mus musculus Azoxymethane-induced colon tumors RNA sequencing

| PRJNA378338 | ENA

Mus musculus breed:FvB

Project description:Mus musculus Azoxymethane-induced colon tumors Exome Sequencing

| PRJNA378336 | ENA

Gene expression profiling of Lgr5 positive cells within intestinal adenomas

Project description:The generation of the Lgr5_EGFP_ires_CreERT2 knock-in mouse allows marking of Lgr5 positive cells of different tissues. Here we use these mice to sort Lgr5 positive cells and their daughter cells form intestinal adenomas and describe the expression profile of these two cell populations. Intestinal adenomas were generated by inducing Apc deletion through tamoxifen injection in Apc_fl/fl-Lgr5_EGFP_ires_CreERT2 mice. In these mice, GFP is expressed under the control of the Lgr5 promoter, leading to highest GFP levels in Lgr5 positive cells (GFP-high). Dividing GFP-high cells pass on Gfp two their daughter cells, thereby diluting the GFP. Daughter cells can therefore be isolated based on their lower GFP positivity (GFP-low). We sorted these two cell fractions (GFP-high and GFP-low) and compared them to each other on 4X44K Agilent Whole Mouse Genome dual colour Microarrays (G4122F). Three independent sorts were performed and RNA of GFP-high cells hybridized directly against RNA of GFP-low cells in three dye swap experiments, resulting in six individual arrays.

2012-08-12 | E-GEOD-37926 | biostudies-arrayexpress

PROX1 mediates chemoresistance-associated recurrence via maintenance of quiescent colon cancer stem cells

Project description:Cancer stem cells (CSCs) are profoundly associated with refractory nature of cancer. A quiescent population of CSCs is responsible for tumorigenesis and chemoresistance in leukemia, whereas neither the presence nor clinical importance of the quiescent CSCs is clearly established in solid tumors. In colon cancer, LGR5 is regarded as a functional marker of CSCs, but heterogeneity among LGR5+ cells was not clearly defined. Here we stratified LGR5+ cells by single-cell gene expression analyses and revealed that a tumorigenic population of mouse LGR5+ cells resides in a quiescent state. We identified 23 signature genes that were uniquely expressed in the quiescent CSCs of mouse tumors, and found that 7 of them were also specifically expressed in a quiescent population of LGR5+ cells in human colon xenograft tumors. Among them, PROX1 was expressed in invasive fronts of colon tumors. PROX1 was induced by TCF1 (TCF7), and the TCF1-mediated PROX1 expression was responsible for not only the maintenance of quiescence but also chemoresistance of colon cancer organoids. Knockout of PROX1 in patient-derived xenograft tumors resulted in inhibition of tumor recurrence after chemotherapeutic treatment. Our data underscore the therapeutic importance of a quiescent CSC population in colon cancer.

2019-11-30 | GSE141157 | GEO

Gene expression in colon cancer stem cells (CSC) cultures identified by Wnt signaling levels

Project description:Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP). 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed. Primary colon CSC cultures with a responsive construct (TOP-GFP): high and low TOP-GFP cell fractions. 12 samples.

2011-11-05 | E-GEOD-33112 | biostudies-arrayexpress

Effects of dietary folic acid on methylation status of colon non-neoplastic epithelium and dysplasia in mice with colitis

Project description:Folic acid supplementation (8 mg/kg diet) promotes colon tumor formation in mice with established colitis induced by carcinogen azoxymethane (AOM) and dextran sulfate sodium sulfate (DSS). This induction of colon tumors was associated with hypomethylation of DNA cased by folic acid supplementation.

2023-09-07 | GSE168975 | GEO

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