THE BITTER TASTE RECEPTOR AGONIST DENATONIUM INHIBITS STEMNESS CHARACTERISTICS IN HEMATOPOIETIC STEM CELLS
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PROVIDER: PRJNA909241 | ENA |
REPOSITORIES: ENA
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Project description:Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (T2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental fluctuation. In the present study, we demonstrated that umbilical cord blood (UCB)-derived CD34+ cells express fully functional T2Rs along with the signal transduction cascade components and their activation by the prototypical agonist, denatonium benzoate, significantly modulated genes involved in stemness maintenance and regulation of cell trafficking. The activation of these specific pathways was confirmed in functional in vitro experiments. Denatonium exposure exerted an antiproliferative effect on UCB-derived CD34+ cells, mainly affecting the most undifferentiated progenitor frequency. It also reduced their clonogenicity and repopulating potential in vitro. In addition, the T2R signaling activation impaired the UCB-derived CD34+ cell trafficking, mainly reducing the migration toward the chemoattractant agent CXCL12 and modulating the expression of the adhesion molecules CD62L, CD49d, and CD29. In conclusion, our results in UCB-derived CD34+ cells expand the observation of T2R expression in the setting of BM resident cells and shed light on the role of T2Rs in the extrinsic regulation of hematopoietic stem cell functions.
2024-01-17 | GSE220210 | GEO
Project description:T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here, using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly cell type specific and lipopolysaccharide (LPS)-induced inflammation increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.
2023-05-25 | GSE213404 | GEO
Project description:Bitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation.
2020-09-07 | GSE149548 | GEO
Project description:Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (TAS2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental fluctuation. In the present study, we demonstrated that umbilical cord blood (UCB)-derived CD34+ cells express fully functional TAS2Rs along with the signal transduction cascade components and their activation by the prototypical agonist, denatonium benzoate, significantly modulated genes involved in stemness maintenance and regulation of cell trafficking. The activation of these specific pathways was confirmed in functional in vitro experiments. Denatonium exposure exerted an antiproliferative effect on UCB-derived CD34+ cells, mainly affecting the most undifferentiated progenitor frequency. It also reduced their clonogenicity and repopulating potential in vitro. In addition, the TAS2R signaling activation impaired the UCB-derived CD34+ cell trafficking, mainly reducing the migration toward the chemoattractant agent CXCL12 and modulating the expression of the adhesion molecules CD62L, CD49d, and CD29. In conclusion, our results in UCB-derived CD34+ cells expand the observation of TAS2R expression in the setting of BM-resident cells and shed light on the role of TAS2Rs in the extrinsic regulation of hematopoietic stem cell functions.
| S-EPMC10787278 | biostudies-literature
Project description:The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional tanycyte subpopulation that expresses key taste transduction genes including bitter taste receptors, the G protein gustducin and the gustatory ion channel TRPM5 (M5). M5 tanycytes have access to blood-borne cues via processes extended towards diaphragmed endothelial fenestrations in the ME and mediate bidirectional communication between the cerebrospinal fluid and blood. This subpopulation responds to metabolic signals including leptin and other hormonal cues and is transcriptionally reprogrammed upon fasting. Acute M5 tanycyte activation induces insulin secretion and acute diphtheria toxin-mediated M5 tanycyte depletion results in impaired glucose tolerance in diet-induced obese mice. We provide a cellular and molecular framework that defines how bitter taste cells in the ME integrate chemosensation with metabolism.
2023-03-01 | GSE226066 | GEO
Project description:An expression profiling was conducted to analyse the effect of the bitter tasting compounds denatonium benzoate (DB) or aloin on the transcriptome of human jejunal crypts compared to DMEM-treated crypts. These two bitter compounds are agonists for the human bitter taste receptor TAS2R43. We took advantage of a deletion polymorphism for TAS2R43, that exists in about 33% of the population to compare the effects of the TAS2R43 agonists in obese subjects that express (TAS2R43(+)) or do not express (TAS2R43(-)) TAS2R43. Primary jejunal crypts from lean (multi-organ donors) or obese (RYGB surgery) subjects were cultured for 24 hours and treated for 4 hours with either DMEM (control) or 1 mM DB or 30 µM aloin. In total 48 mRNA samples were subjected to RNAseq analysis.
2021-11-23 | GSE186509 | GEO
Project description:Denatonium as a bitter taste receptor agonist modifies transcriptomic profile and functions of acute myeloid leukemia cells
| PRJNA629046 | ENA
Project description:<p>The goal of this project is to determine variation in human bitter perception and the effectiveness of bitter blockers in individuals of different genotypes. The project is based on the parent project titled "Efficacy of bitter taste blockers on flavor acceptance in pediatric population", which addresses how bitter taste perception affects medication compliance. As a part of the parent project, mothers and their children were recruited from the general population of metropolitan Philadelphia through print and internet media as well as from a database of past research participants. Adults (mothers) were evaluated in the laboratory for bitter taste perception for a variety of "Generally Recognized As Safe" (GRAS) bitter compounds using the general Labeled Magnitude Scale (gLMS) which allows subjects to rate sensory intensity. Mothers were also evaluated for perception of the liquid formulation of the drug Kaletra<sup>TM</sup>, a recommended 1st line treatment for infants with HIV infection, whose taste is rejected by some children and accepted well by others. DNA samples from mothers were genotyped as a part of this study to identify (1) novel genes associated with human bitter perception and (2) the ability of compounds to block bitterness.</p>
| phs000839 | dbGaP
Project description:Taste buds are complex sensory organs that are embedded in the epithelium of fungiform papillae (FP) and circumvallate papillae (CV). The sweet, bitter, and umami taste are sensed by type II taste cells that expressed taste receptors (Tas1rs and Tas2rs) which coupled with taste G-protein α-gustducin. Recent studies revealed that the taste response profiles of α-gustducin-expressing cells are different between FP and CV. We applied the high-throughput single-cell RNA-sequencing combined with fluorescence-activated cell sorting (FACS) to profile the transcriptome of the α-gustducin-expressing taste cells in both fungiform and circumvallatae papillae with transgenic mice expressing green fluorescent protein (GFP).
2021-08-01 | GSE169191 | GEO
Project description:Inflammation induces bitter taste oversensitization via epigenetic changes in Tas2r gene clusters
| PRJNA880809 | ENA