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Denatonium as a bitter taste receptor agonist modifies transcriptomic profile and functions of acute myeloid leukemia cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149548 | GEO | 2020/09/07

REPOSITORIES: GEO

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Inflammation induces bitter taste oversensitization via epigenetic changes in Tas2r gene clusters

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.

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THE BITTER TASTE RECEPTOR AGONIST DENATONIUM INHIBITS STEMNESS CHARACTERISTICS IN HEMATOPOIETIC STEM CELLS

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Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity

Project description:Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity

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| phs000839 | dbGaP

High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro

Project description:Taste buds on the tongue are collections of taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice. However, SOX2 is variably expressed among CVP cells suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show highly expressing SOX2+ cells are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium, while organoids derived from low-expressing SOX2+ progenitors are composed entirely of non-taste cells. Hedgehog and WNT/ß-catenin are required for taste homeostasis in adult mice, but only WNT/ß-catenin promotes TRC differentiation in vitro and does so only in organoids derived from higher SOX2+ taste lineage-competent progenitors.

2023-02-07 | GSE207624 | GEO

Denatonium as a bitter taste receptor agonist modifies transcriptomic profile and functions of acute myeloid leukemia cells

Project description:Denatonium as a bitter taste receptor agonist modifies transcriptomic profile and functions of acute myeloid leukemia cells

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EGR4 is critical for cell-fate determination and maintenance of Geniculate Ganglion neurons underlying sweet and umami taste

Project description:The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations, BRN3A+ somatosensory neurons that innervate the pinna, and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, much less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3-6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes, and upregulate BRN3A. This is followed by a severe loss of chemosensory innervation of taste buds, a loss of Type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in Type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.

2023-02-01 | GSE223724 | GEO

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