Lgr5+tuft marker+ intestinal tumor cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118853 | GEO | 2021/02/19
REPOSITORIES: GEO
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Project description:Lgr5+tuft marker+ intestinal tumor cells
| PRJNA487052 | ENA
Project description:In our study, we investigated the effect of muscarinic receptor blockade on murine intestinal stem cell activity and differentiation. Following pharmacologic (scopolamine) and genetic muscarinic receptor interruption (M3R-KO, M1R-KO; Vil-Cre x M3R fl/fl, Vil-Cre x M1R fl/fl mice, respectively), we observe a selective, significant expansion of DCLK1-positive tuft cells. This is primarily sensed by endocrine Prox1-positive cells (Prox1-CreERT2 x M3R fl/fl mice), while Lgr5-positive ISCs respond with a reduction of their cellular activity (Lgr5-EGFP-IRES-CreERT2 x M3R fl/fl mice). To characterize expanding tuft cells in more detail, adult BAC transgenic DCLK1-DTR-ZSgreen reporter mice generated in our lab were treated with scopolamine or sodium chloride as controls (Sham) for 7d and live jejunal EPC-positive/ZSgreen-positive cells sorted. Extracted total RNA from sorted ZSgreen-positive cells of scopolamine- and sham-treated mice was sequenced. Further analysis revealed that expanding tuft cells orchestrate an increase in mucosal acetylcholine, which maintained intracellular signaling pathways such as p-ERK/ERK 1/2 or TCF-1/7. Finally, acute irradiation injury was employed to investigate the importance of this regulatory circuit for tissue homeostasis. Indeed, tissue injury in Vil-Cre x M3R fl/fl mice resulted in a severe reduction of epithelial DCLK1-positive tuft cells, concomitant to reduced mucosal Ach levels as well as intracellular PI3K-/p-ERK levels. Therefore, DCLK1-positive tuft cells appear essential for the maintenance of a regular intestinal cholinergic niche.
2019-11-01 | GSE138365 | GEO
Project description:Dclk1 expression defines a rare population of cells in normal pancreas whose frequency is increased at early stages pancreatic tumors. The identity and the precise roles of Dclk1 expressing cells in pancreas are matter of debate, although the concept of their involvement in a number of key functions, including regeneration and neoplasia, has emerged. We employed a novel Dclk1 reporter mouse model and single cell RNAseq analysis to define Dclk1 expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas, Dclk1 epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia, Dclk1 expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells represent the main ones. These cells play opposing roles in pancreatic neoplasia, with Dclk1+ ADM-like cells sustaining tumor growth and Dclk1+ tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1+ tuft-like cells requires the activation of SPIB and is further supported by a cellular loop involving cancer group 2 innate lymphoid cells (ILC2) and activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1+ tuft-like cells release angiotensinogen that play protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1+ cells in normal pancreas and also unveils a protective axis against pancreatic neoplasia involving Dclk1+ tuft-like cells, ILC2 and CAFs, which ultimately results in angiotensinogen release.
2024-10-08 | GSE259357 | GEO
Project description:Dclk1 expression defines a rare population of cells in normal pancreas whose frequency is increased at early stages pancreatic tumors. The identity and the precise roles of Dclk1 expressing cells in pancreas are matter of debate, although the concept of their involvement in a number of key functions, including regeneration and neoplasia, has emerged. We employed a novel Dclk1 reporter mouse model and single cell RNAseq analysis to define Dclk1 expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas, Dclk1 epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia, Dclk1 expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells represent the main ones. These cells play opposing roles in pancreatic neoplasia, with Dclk1+ ADM-like cells sustaining tumor growth and Dclk1+ tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1+ tuft-like cells requires the activation of SPIB and is further supported by a cellular loop involving cancer group 2 innate lymphoid cells (ILC2) and activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1+ tuft-like cells release angiotensinogen that play protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1+ cells in normal pancreas and also unveils a protective axis against pancreatic neoplasia involving Dclk1+ tuft-like cells, ILC2 and CAFs, which ultimately results in angiotensinogen release.
2024-10-08 | GSE259356 | GEO
Project description:Accumulating evidence has shown the existence of tumor stem cells, and many researchers and clinicians are focusing on the therapeutic potential of targeting tumor stem cells. Previously, we reported that doublecortin like kinase 1 (Dclk1) marks tumor stem cells but not normal stem cells in ApcMin/+ mouse intestine, and that selective ablation of Dclk1+ cells results in collapse of the intestinal tumors without any apparent damages in the normal mucosa. Here, we sought to clarify gene expresion profile of Dclk1+ cells by microarray analyses in mouse normal intestinal epithelium and ApcMin/+ mouse intestinal tumors. Microarray analyses demonstrated that genes related to microtubules and actin cytoskeleton (e.g., Rac2) were highly expressed in Dclk1+ normal intestinal and tumor cells. We found the expression of Src family kinases (i.e., Hck, Lyn, Csk, and Ptpn6) in Dclk1+ normal intestinal and tumor cells.
2017-06-05 | GSE99387 | 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: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: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:Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer. Here we show that DCLK1 expression in the gastric cancer cell line MKN1 impacts EV biogenesis both quantitatively and qualitatively in a kinase dependent manner, revealing a hitherto unknown role for this putative oncogenic kinase. Importantly, the proteome of EVs isolated from DCLK1 expressing gastric cancer cells is enriched for proteins involved in tumor-promoting biological processes, raising the prospect of establishing DCLK1 as a novel anti-cancer target.
2021-03-23 | PXD021371 | Pride
Project description:A comparative bulk cell RNA-seq analysis of diverse intestinal stem cell populations was performed, for cells expressing the following markers: Lgr5-eGFPhi, Cd166+, Cd24lo, Grp78, upper side population (SP), Bmi1, mTert, Hopx, Dclk1, a lower side population (SP)
2017-07-10 | GSE99815 | GEO