Transcriptomic comparison between LGR5 and POLI double tumor cell populations in CRC
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PROVIDER: PRJNA607725 | ENA |
REPOSITORIES: ENA
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Project description:A transcriptomic comparative analysis was performed to explore and characterize in terms of gene expression and biological pathways the different LGR5 and POLI population from colorectal tumor xenografts.
2020-05-22 | GSE145603 | GEO
Project description:Colorectal cancer tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is unknown. Using CRC patient derived organoids (PDOs), we found that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.
2023-12-20 | GSE247359 | GEO
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
Project description:To follow the changes in the transcriptional programs accompanying the specification of the embryonic Lgr5+ cells we sequenced whole transcriptomes of embryonic intestinal epithelium progenitors (at E13.5 and E15.5). EpCAM positive embryonic gut epithelium was isolated from dissected small intestines using fluorescence activated cell sorting (FACS). Lgr5+ progenitors were purified on the basis of GFP fluorescence from Lgr5GFP-Cre-ERT mice (Barker et al. 2007). Double positive embryonic progenitors were isolated by FACS based on GFP and tdTomato fluorescence.
2019-09-24 | GSE104727 | GEO
Project description:In normal intestine, Lgr5 are a pool of rapidly dividing stem cells that gives rise to the whole intestinal crypts. Here we have labelled both Lgr5 and Ki67 genes with fluorescent markers by means of CRISPR/Cas9 in human patient derived organoids (PDO).
2017-04-28 | GSE92961 | GEO
Project description:Purpose: The goal of the study was to investigate the effect of Neuregulin 1 (NRG1) on intestinal crypt-based columnar stem cells, their progenitors and differentiated cells. Methods: Lgr5-EGFP C57BL/6 male mice (11-15 week-old, littermates) were injected with two intra-peritoneal doses of NRG1 daily (7.5 µg every 12 hours) or vehicle control (PBS) for 5 days (n=3). On day 6, small intestinal tissues were collected and several intestinal cell populations isolated by FACS based on Lgr5-GFP and CD24 expression [CBC stem cells (Lgr5high-CD24low), their immediate progenitors (Lgr5med-CD24low), subsequent progenitors (Lgr5low-CD24low) and differentiated cells (double negative)]. RNA was then extracted for each cell population and RNA sequencing analysis conducted.
2020-07-13 | GSE149311 | GEO
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.
2013-04-19 | GSE46200 | GEO
Project description:Cancer stem cells (CSCs) are a minority population of cancer cells that display stem cell-like multipotent and self-renewal properties. They give rise to the bulk of cancer cells with limited replicative potential. In colorectal cancer (CRC), CSCs are marked by expression of the leucine-rich repeat-containing G-protein receptor 5 (Lgr5). Since CSCs display multipotent and self-renewal properties, this population is thought to seed metastases. Here, we used a mouse model and human xenografts to investigate the cell-of-origin of metastases. Surprisingly, we found that most CRC cells that disseminated and entered the blood circulation were Lgr5-. Lgr5- cancer cells arriving at the metastatic site formed lesions in which Lgr5+ CSCs appeared. This plasticity could occur independently of stemness-inducing factors, and was an indispensable event for the outgrowth of metastases, since neutralization of this plasticity prevented metastatic outgrowth. Combined, our study shows that most metastases are seeded by Lgr5- cancer cells, and that these cells have a niche-independent and intrinsic capacity to become CSCs and restore epithelial hierarchy.
2020-03-18 | GSE143988 | GEO
Project description:Transcriptome profiling using Affymetrix GeneChip arrays was performed on sorted populations of Lgr5-expressing mouse ovarian surface epithelium. The ovary surface epithelium (OSE) undergoes ovulatory tear-and-remodelling throughout life. Resident stem cells drive such tissue homeostasis in many adult epithelia, but their existence in the ovary has yet to be definitively proven. Lgr5 marks stem cells in multiple epithelia. Here we use reporter mice and Single Molecule Florescent-in-Situ-Hybridization (FISH) to document candidate Lgr5+ stem cells within the mouse ovary and associated structures. Lgr5 is broadly expressed during ovary organogenesis, but becomes limited to the OSE in early neonate life. In adults, Lgr5 expression is predominantly restricted to proliferative regions of the OSE and fimbria- mesovarian junction. Using conditional in vivo lineage tracing we identify embryonic and early neonate Lgr5+ populations as stem/progenitor cells contributing to the development of adult OSE and granulosa cell lineages, as well as the epithelia of the mesovarian and oviduct including its distal opening, fimbria. Long-term lineage tracing reveals that adult OSE-resident Lgr5+ populations contribute to epithelial homeostasis and OSE regenerative repair in vivo. Thus, Lgr5 is a marker of stem/progenitor cells of the ovary and tubal epithelia. Ovarian surface epithelium from pooled batches of Lgr5-eGFP-CreERT2 mice (n=8, per array) were sorted for cells expressing either high or low EGFP. Total RNA from three technical replicates per sorted population (Lgr5-high or Lgr5-low) was extracted with the RNeasy Micro Kit (QIAGEN), DNaseI-treated, and amplified with the Ovation Pico WTA V2 (NuGEN Technologies). Single-stranded cDNA amplification products were purified using QIAquick PCR Purification Kit (QIAGEN). cDNA was biotinylated using the Encore Biotin Module (NuGEN Technologies). Biotiylated cDNA was hybridized to Affymetrix Mouse Genechip ST 2.0 expression arrays.
2013-12-04 | E-GEOD-52925 | biostudies-arrayexpress