Tissue tuft cell mRNA sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE114067 | GEO | 2018/05/05
REPOSITORIES: GEO
Similar Datasets
Project description:The goal of the study was to sequence mRNA from tuft cells (identified as CD45-;EpCAM+;IL-25+ using Flare25 reporter mice) in the epithelia of thymus and small intestine. As a control, non-tuft epithelial cells (CD45-;EpCAM+;IL-25-) were also isolated. The data were used to compare tuft cell markers between the small intestine and thymus.
2018-05-19 | GSE114668 | GEO
Project description:The goal of the study was to sequence mRNA from tuft cells (identified as CD11c-;CD45-;EpCAM+;IL-25+ using Flare25 reporter mice) in C57BL/6 and Aire-/- mice. The data were used to investigate thymic tuft cell heterogeneity with and without AIRE protein expression.
2018-06-03 | GSE114895 | GEO
Project description:Aeroallergen sensing by airway epithelial cells can trigger pathogenic immune responses leading to chronic type 2 inflammation, the hallmark of airway diseases such as asthma. Airway tuft cells are specialized chemosensory epithelial cells and the dominant source of the epithelial cytokine IL-25 in the trachea and of cysteinyl leukotrienes (CysLTs) in the naïve murine nasal mucosa. How IL-25 and CysLTs might cooperatively promote type 2 inflammation in the airways has not been clarified. Here, we showed that inhalation of LTC4 in combination with a subthreshold dose of IL-25 led to dramatic synergistic induction of type 2 inflammation throughout the lungs, causing rapid eosinophilia, inflammatory type 2 innate lymphoid cell (ILC2) proliferation and type 2 cytokine production, dendritic cell (DC) and CD4+ T cell recruitment and goblet cell hyperplasia. While lung eosinophilia was dominantly mediated through the classical CysLT receptor CysLT1R, type 2 cytokines and activation of innate immune cells required signaling through both CysLT1R and CysLT2R. Tuft cell-specific deletion of Ltc4s, the terminal enzyme required for CysLT production, reduced lung inflammation and the systemic immune response after inhalation of the mold aeroallergen Alternaria; this effect was further enhanced by concomitant blockade of IL-25. Our findings identified a potent synergy of CysLTs and IL-25 downstream of aeroallergen-trigged activation of airway tuft cells leading to a highly polarized type 2 immune response and further implicate airway tuft cells as powerful modulators of type 2 immunity in the lungs.
2021-12-25 | GSE188820 | GEO
Project description:We performed Smart-seq2 scRNAseq on 156 pancreatic tuft cells . We also profiled FACS sorted EpCAM+;CD45+ immune cells and EpCAM-;CD45- non-immune stroma cells from from 3 caerulein-treated KC and 2 caerulein-treated KPouC pancreata by using the 10X Genomics 3' scRNAseq v3.1 kit.
2020-07-13 | GSE154259 | GEO
Project description:While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5+ dysplastic regions after influenza injury. Using bulk and single cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4Ra signaling are required to drive tuft cell development in dysplastic/injured lungs. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5+ dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5+ cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease.
2022-09-14 | GSE197156 | GEO
Project description:While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5+ dysplastic regions after influenza injury. Using bulk and single cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4Ra signaling are required to drive tuft cell development in dysplastic/injured lungs. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5+ dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5+ cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease.
2022-09-14 | GSE197162 | GEO
Project description:Intestinal tuft cells are critical in anti-helminth immunity by producing IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) in order to ultimately expand both goblet and tuft cells. Translational reprogramming is involved in intestinal tuft cell differentiation but the role of tRNA modifications in this process is unknown. We show here that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of N. brasiliensis infection in mice. Elp3 is essential for the IL-13-dependent induction of some glycolytic enzymes such as Hexokinase 1 and Aldolase A and consequently links specific metabolic pathways to tuft cell differentiation. Importantly, loss of epithelial Elp3 in the intestine blocks the translation of Nprl2, a mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in both transit amplifying and progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation and impairs the control of intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cell differentiation and provide insights into mechanisms through which some tRNA modifications promote a type 2 immune response to parasites in the intestine.
2024-07-25 | GSE241625 | GEO
Project description:Intestinal homeostasis is dynamically coordinated by various types of epithelial cells fulfilling their specific functions. Tuft cells as chemosensory cells have emerged as key players of the host response, such as innate immunity. Tuft cells are also critical for the restoration of intestinal architecture upon damage, thereby contributing to inflammatory bowel diseases (IBDs) characterized by defective intestinal barrier integrity. However, the molecular mechanism of how tuft cell homeostasis is controlled remains obscure. Recent studies have identified single-nucleotide polymorphisms in the inositol polyphosphate multikinase (IPMK) gene associated with IBD predisposition. IPMK, an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. To investigate the functional significance of IPMK in gut epithelium, we generated intestinal epithelial cell (IEC)-specific Ipmk knockout (IPMKΔIEC) mice. Whereas IPMKΔIEC mice developed normally and showed no intestinal abnormalities during homeostasis, Ipmk deletion aggravated dextran sulfate sodium (DSS)-induced colitis, with higher clinical colitis scores, and elevated epithelial barrier permeability. Surprisingly, no apparent defects in epithelial growth signaling pathway and inflammation were found in DSS-challenged, IPMK-deficient colons. Rather, Ipmk deletion led to a significant decrease in the number of tuft cells without influencing other intestinal epithelial cells. Ipmk deletion in the gut epithelium was found to reduce choline acetyltransferase but not cytokines (e.g., IL-25), suggesting selective loss of cholinergic signaling. Single-cell RNA-sequencing of mouse colonic tuft cells (EpCAM+/Siglec F+) and immunohistochemistry revealed three populations of tuft cells and further showed that, in IPMKΔIEC mice, a transcriptionally inactive tuft club cell population was markedly expanded, and neuronal-related tuft cells were relatively decreased, supporting the abnormal development of tuft cells without IPMK functions. Thus, IPMK acts as a physiological determinant of colonic tuft cell homeostasis, thereby mediating tissue regeneration upon injury.
2022-10-26 | GSE200284 | GEO
Project description:In mice, intestinal tuft cells have been described as a long-lived, post-mitotic cell type of which two distinct subsets have been identified, named tuft-1 and tuft-2.By combining analysis of primary human intestinal resection material with organoid technology, we identify four distinct states of human tuft cells, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that its numbers rapidly increase upon interleukin (IL)-4 and IL-13 exposure, as reported previously in mouse. This, however, is induced through proliferation of pre-existing tuft cells, rather than through increasedde novo generation from stem cells. Indeed, proliferative tuft cells occurin vivoboth in adult and in fetal human intestine. Single mature proliferating Tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem- and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans.
2024-05-01 | GSE233451 | 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