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. 2014 Jun 14:2:212-5.
doi: 10.1016/j.gdata.2014.06.005. eCollection 2014 Dec.

Transcriptome profiling of LGR5 positive colorectal cancer cells

Daniela Hirsch  1 , Yue Hu  2 , Thomas Ried  2 , Roland Moll  3 , Timo Gaiser  4
Affiliations

Transcriptome profiling of LGR5 positive colorectal cancer cells

Daniela Hirsch et al. Genom Data. .

Abstract

The concept of cancer stem cells (CSCs) claims that colorectal carcinomas (CRCs), like normal colorectal epithelium, are organized hierarchically and contain a subpopulation of qualitatively distinct cancer cells. The expression of distinctive surface markers or of certain enzymes is a prerequisite for the isolation and characterization of the CSC population. With respect to CRCs, putative CSCs can be identified by leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5, also known as G-protein-coupled receptor 49, Gpr49). However, the precise function of the intestinal stem cell marker Lgr5 in CRCs remains largely unknown. We silenced LGR5 expression in SW480 CRC cells via lentiviral shRNA constructs. This led to the depletion of a morphologically distinct subpopulation of SW480 CRC cells. Microarray gene expression profiling revealed a down-regulation of NOTCH signaling upon LGR5 silencing that could be confirmed by immunohistochemistry. Furthermore, we induced inflammation-driven colon tumors in Lgr5-EGFP-IRES-Cre-ERT2 mice via administration of azoxymethane and dextrane sodium sulfate. The induced tumors were flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. Lgr5 high tumor cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal stem cells. Here we provide a thorough description of our two gene expression datasets including quality control checks uploaded to Gene Expression Omnibus database (data accession number: GSE46200). The analysis and interpretation of our gene expression data and related results have been published recently by Hirsch and colleagues in Carcinogenesis in 2014.

Keywords: Colorectal cancer; Expression profiling; Lgr5.

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Figures

Fig. 1
Fig. 1
Workflow of flow sorting AOM/DSS-induced mouse colon tumors for Lgr5. Colon tumor region is circled.
Fig. 2
Fig. 2
Ingenuity pathway analysis reveals an up-regulation of the NOTCH pathway in LGR5 high SW480 spheres compared to LGR5 low SW480 adherent cells. Red, genes up-regulated in LGR5 high spheres; green, genes down-regulated in LGR5 high spheres. The intensity of the color is correlated with fold change. All color labeled genes show a > threefold differential expression and pass a threshold of FDR < 0.05.
Fig. 3
Fig. 3
Principal component analysis shows a well separation between normal colons and AOM/DSS-induced tumors. Also, there is a well separation between Lgr5 high and low tumor cells. The separation between Lgr5 high and low normal colon cells is less pronounced. Paired Lgr5 high and low samples are linked by lines.
See this image and copyright information in PMC

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