Expression data from mouse proximal intestinal epithelial Lgr5(hi) stem cells and differentiated villus cells (enterocytes from Atoh1 conditional knockout)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE41541 | GEO | 2012/10/13
SECONDARY ACCESSION(S): PRJNA177387
REPOSITORIES: GEO
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Project description:We used microarrays to detail the differentail gene expression between intestinal Lgr5(hi) stem cells and differentiated cells Assay the differential gene expression using total RNA from flow cytometry sorted Lgr5(hi) cells and EDTA isolated enterocytes from Atoh1 conditional knockout
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Project description:The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5, a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5+ villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis.
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Project description:Lgr5+ telocytes are a signaling hub at the intestinal villus tip
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Project description:The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.
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Project description:We previously identified Dclk1, a tuft cell marker, marks tumor stem cells (TSCs) in mouse intestinal tumors. In this study, we have identified IL17RB as a cell surface marker distinctively expressed by Dclk1+ tuft-like tumor cells in mouse intestinal tumors. Using this tuft cell marker, we compared and analyzed the transcriptome of Lgr5-tuft marker-, Lgr5+tuft marker-, Lgr5-tuft marker+, and Lgr5+tuft marker+ tumor cells. These analyses revealed that tuft-like tumor cells in the intestinal tumors comprise two distinct subsets: highly differentiated tuft-like tumor cells (Lgr5-tuft marker+ cells) and tuft-like tumor cells with TCS potential (Lgr5+tuft marker+ cells).
2021-02-19 | GSE118853 | GEO
Project description:Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Validated markers of these early stem/progenitor populations are essential for deciphering their in vivo function and for evaluating their clinical potential for treating adult kidney disease. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5+ve cells via in vivo lineage tracing. The appearance and localization of Lgr5+ve cells coincided with that of the S-shaped body around E14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until P7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a novel progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Metanephric kidneys of timed pregnancies of ~14 days of gestation were harvested and cultured for ~10 days. Lgr5-EGFP-Ires-CreERT2-positive embryonic kidneys were identified by fluorescence microscopy and enzymatically digested to a single cell solution. GFPhi and GFPneg cells were sorted by flow cytometry (MoFlo; Dako). RNA, isolated using RNeasy (Qiagen), was analyzed using the Affymetrix platform.
2012-09-04 | E-GEOD-39881 | biostudies-arrayexpress
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: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