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.
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).
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.
Project description:We generated 95.37 Gb of high-quality sequencing data (~7.95 Gb per sample). The analysis showed differences of transcriptomes between the common white sweet quinoa and the yellow bitter quinoa. We identified numerous differentially expressed genes that exhibited distinct expression patterns. These genes have known or potential roles in taste of quinoa fruit.Therefore, we are appealing candidates for further investigation of the gene expression and associated regulatory mechanisms related to the accumulation of bitter saponins in C. quinoa fruits.
Project description:The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor involved in sweet-taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions regulated by the sweet-taste perception system, we hypothesized that a disruption of the sweet-taste perception in the brain could have a key role in the development of cognitive dysfunction. To assess the importance of the sweet-taste receptors in the brain, we conducted transcriptomic and proteomic analyses of cortical and hippocampal tissues isolated from T1R3 knock-out (T1R3KO) mice. The effect of an impaired sweet-taste perception system on cognition functions were examined by analyzing synaptic integrity and performing animal behavior on T1R3KO mice. Although T1R3KO mice did not present a metabolically disrupted phenotype, bioinformatic interpretation of the high-dimensionality data indicated a strong neurodegenerative signature associated with significant alterations in pathways involved in neuritogenesis, dendritic growth, and synaptogenesis. Furthermore, a significantly reduced dendritic spine density was observed in T1R3KO mice together with alterations in learning and memory functions as well as sociability deficits. Taken together our data suggest that the sweet-taste receptor system plays an important neurotrophic role in the extralingual central nervous tissue that underpins synaptic function, memory acquisition, and social behavior.
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.
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.
Project description:Sensory receptors, including olfactory receptors, taste receptors, and opsins have recently been found in a variety of non-sensory tissues where they have distinct physiological functions. As G protein-coupled receptors, these proteins can serve as important chemosensors by sensing and interpreting chemical cues in the environment. We reasoned that the liver, the largest metabolic organ in the body, is primed to take advantage of some of these sensory receptors in order to sense and regulate blood content and metabolism. In this study, we designed a custom TaqMan array to screen for all bitter, sweet, and umani taste receptors, the non-visual optins, and 44 olfactory receptors in the murine liver.
Project description:The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled or fermented foods. Taste and somatosensory receptors in the oral cavity trigger aversive behaviors in response to acid stimuli. Here we show that the ion channel Otopetrin-1, a proton-selective channel normally involved in the sensation of gravity in the vestibular system, is essential for sour-sensing in the taste system. We demonstrate that a knockout of Otop1 eliminates acid responses from sour-sensing taste-receptor-cells (TRCs). In addition, we show that mice engineered to express otopetrin-1 in sweet TRCs now have sweet cells that also respond to sour stimuli. Next, we genetically identified the taste ganglion neurons mediating each of the five basic taste qualities, and demonstrate that sour taste uses its own dedicated labeled line from TRCs in the tongue to finely tuned taste neurons in the brain to trigger aversive behaviors.
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>