Lgr5+tuft marker+ intestinal tumor cells
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ABSTRACT:
PROVIDER: PRJNA487052 | ENA |
REPOSITORIES: ENA
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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:Tuft cells as a type of intestinal epithelial cells exist in epithelial barriers that play a critical role in immunity against parasite infection. It remains elusive about whether Tuft cells participate in bacterial eradication. Here we identify Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Tuft-2 cells are derived from Lgr5+ intestinal stem cells but not bone marrow cells. Depletion of Tuft-2 cells is susceptible to bacterial infection. Tuft-2 cells quickly expand over bacterial infection and sense bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engagement with N-undecanoylglycine activates GPCR-PLCγ2-Ca2+ signal axis, which initiates prostaglandin D2 (PGD2) production. PGD2 enhances mucus secretion of Goblet cells and induces antibacterial immunity. Moreover, Vmn2r26 signaling also promotes SpiB expression, which is responsible for Tuft-2 cell development and expansion over bacterial challenge. Our findings reveal a novel function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites. We used microarrays to detail the gene expression of Tuft-2 cells compared with non Tuft-2 epithelial cells under Shigella infection.
2021-09-24 | GSE184675 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE249744 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE242118 | GEO
Project description:RNAseq of coding and noncoding RNA isolated from intestinal tuft cells reveals murine rotavirus replication in intestinal tuft cells.
2021-10-04 | GSE168773 | GEO
Project description:The identification of Lgr5 as an intestinal stem cell marker has made it possible to isolate and study primary stem cells from small intestine and skins. Applying genome-wide resequencing of bisulfite-treated genomic DNA, we profiled the DNA methylation changes of FACS-sorted Lgr5+ve stem cells and their immediate undifferentiated daughter cells from small intestine and skin. In addition to this, we also analyzed terminally differentiated villus cells. We find that terminal differentiation of an adult solid-tissue stem cell does not require DNA methylation dynamics at transcriptional start sites, but is characterized by hypo-methylation of enhancer-like domains. We used cell fractions of intestines from Lgr5-EGFP-ires-CreERT2 mice, expressing GFP under the control of the Lgr5 promoter. RNA was isolated from several FACS-sorted cell populations, one expressing GFP at high levels (GFPhi) and the other expressing GFP at low levels (GFPlow), both from small intestine and skin. We also isolated RNA from intestinal epithelial villus cells. Differentially labelled cRNA from GFPhi, GFPlow and villus cells from three different sorts (each combining three different mice) were hybridized on Affymetrix HT MG-430 PM arrays.
2013-04-25 | E-GEOD-46303 | 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:Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of intestinal epithelium. The regulatory mechanism of ISCs is not fully understood. Here we report that CREPT, a recently identified tumor-promoting gene, is preferably expressed in the crypts, where the ISCs reside, but not in the villi. The Lgr5+ ISCs have much higher CREPT protein level than Lgr5- cells. To explore the function of CREPT in ISCs, we isolated WT and CREPT deleted Lgr5+ ISCs (Lgr5-CREPTKO) to perform Next generation sequencing.
2020-11-08 | GSE143604 | GEO
Project description:Stomach and intestinal adult epithelia harbor stem cells that are responsible for their continuous regeneration. Stomach and intestinal stem cells differ in their differentiation program and in the gene repertoire that they express. We show that single adult Lgr5-positive stem cells, isolated from 3D cultured small intestinal organoids, require Cdx2 to maintain their intestinal identity and are converted cell-autonomously into stomach-pyloric stem cells in the absence of this transcription factor. In order to obtain Cdx2null intestinal stem cells carrying the Lgr5-EGFP marker, 5-6 days old small intestinal organoids generated from Cdx2-/fl/Lgr5-EGFP-Ires-CreERT2 mice were incubated with 1 µM of 4-hydroxytamoxifen in intestinal culture medium for 16h to activate the Cre recombinase. Controls were 4-hydroxytamoxifen-untreated small intestinal (Control SI) and stomach (Control Sto) organoids issued from mice with the same genotype. The organoids were dissociated and sorted for EGFPhi. Cdx2null, Control SI and Control Sto clonal organoids were generated and expanded from Lgr5-EGFPhi single cells in stomach specific culture medium (ENRWfg) and RNA was isolated for RNA-Seq analysis. Cdx2+ Stomach (Sto) organoids were generated by infection of the wild type stomach organoids with lentiviral stock expressing Cdx2. They were cultured in stomach medium (ENRWfg) and RNA was isolated for RNA-Seq analysis
2014-12-05 | E-GEOD-62784 | biostudies-arrayexpress
Project description:Lgr5+ crypt base columnar cells, the operational intestinal stem cells (ISCs), are thought to be dispensable for small intestinal (SI) homeostasis. Using a novel Lgr5-2A-DTR (Diphtheria Toxin Receptor) model which ablates Lgr5+ cells with near-complete efficiency and retains endogenous levels of Lgr5 expression, we show that persistent depletion of Lgr5+ ISCs in fact compromises SI epithelial integrity and reduces epithelial turnover in vivo. In vitro, Lgr5-2A-DTR SI organoids are unable to establish or survive when Lgr5+ ISCs are continuously eliminated when DT is in the media. However, transient exposure to DT at the start of culture allows organoids to form, and the rate of outgrowth reduces with increasing length of DT presence. Our results indicate that intestinal homeostasis requires a constant pool of Lgr5+ ISCs, which is supplied by rapidly reprogrammed non-Lgr5+ crypt populations when pre-existing Lgr5+ ISCs are ablated.
2020-12-31 | GSE148727 | GEO