Tuft cells act as regenerative stem cells in the human intestine
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ABSTRACT:
PROVIDER: PRJNA976291 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24738155_1.fastq.gz | Fastqsanger.gz | |||
| SRR24738155_2.fastq.gz | Fastqsanger.gz | |||
| SRR24738156_1.fastq.gz | Fastqsanger.gz | |||
| SRR24738156_2.fastq.gz | Fastqsanger.gz | |||
| SRR24738157_1.fastq.gz | Fastqsanger.gz |
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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:Rare chemosensory epithelial cells called tuft cells have known roles in small intestinal regulation of type 2 cytokine producing Group 2 innate lymphoid cells. To understand the phenotype of tuft cells in another tissue, the extrahepatic biliary tree, we performed RNAseq analysis on tuft cells and non-tuft epithelial cells from small intestine and gallbladder of the mouse.
2022-03-01 | GSE194035 | GEO
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 CD45-;EpCAM+;IL-25+ using Flare25 reporter mice) in the epithelia of 5 different murine tissues: trachea, thymus, colon, gall baldder, small intestine. As a control, non-tuft epithelial cells (CD45-;EpCAM+;IL-25-) were also isolated. The data were used to identify differentially expressed genes across tuft cells from different tissues and to define a transcriptional tuft cell "signature" that is common to all tissues analyzed but absent in the non-tuft epithelial cells.
2018-05-05 | GSE114067 | GEO
Project description:Tuft cells are an epithelial cell subset critical for initiating type 2 immune responses to parasites and protozoa in the small intestine. To respond to these stimuli, intestinal tuft cells use taste chemosensory signaling pathways, but the role of taste receptors in type 2 immunity is poorly understood. Here, we show that the taste receptor TAS1R3, which detects sweet and umami in the tongue, also regulates tuft cell responses in the distal small intestine. BALB/c mice, which have an inactive form of TAS1R3, as well as Tas1r3-deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum including the protozoa Tritrichomonas muris and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth Heligmosomoides polygyrus, which infects the proximal small intestine. Examination of uninfected Tas1r3-/- mice revealed a modest reduction in the number of tuft cells in the proximal small intestine but a severe decrease in the distal small intestine at homeostasis. Together, these results suggest that TAS1R3 influences intestinal immunity by shaping the epithelial cell landscape at steady state.
2020-01-09 | GSE140395 | 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:Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the “weep” response that is critical for Type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate Type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft-cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal Type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.
2024-05-02 | GSE262198 | GEO
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: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