Effect of deficiency of TAS1R3 on testicular gene expression in male mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE226995 | GEO | 2024/02/07
REPOSITORIES: GEO
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Project description:Recent studies suggest that the western diet negatively affects male reproduction, but few underlying molecular mechanisms have been established. Also, several studies have reported TAS1R3 is expressed in testis, epididymis and sperm, but their role in male reproduction remains unknown. To investigate the function of taste receptor TAS1R3 in the male reproductive function under western diet condition, we performed RNA-sequencing analysis on testes from C57BL/6 mice fed long-term (18 weeks) western diet.
2024-12-19 | GSE221433 | GEO
Project description:To investigate whether taste receptor type 1 member 3 (TAS1R3) might serve as a key modulator of cognitive impairment led by WD-induced obesity, male Tas1r3-wild type (WT) and knockout (KO) mice were randomized to receive either a normal diet (ND) or western diet (WD) for 18 weeks. We performed gene expression profiling analysis using data obtained from RNA-seq of hippocampus of two WT mice fed a WD (WT-WD) and two KO-WD mice.
2024-10-11 | GSE215332 | 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:Accumulating studies support that the western diet (WD), a diet comprised of saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety, remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) is identified in the hypothalamus, a key brain area involved in both sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the role of the hypothalamic TAS1R3 in WD-induced anxiety using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. We evaluated anxiety levels with the open field test and the elevated plus maze test. Behavior tests showed WD increased anxiety in WT mice, whereas Tas1r3-/- mice were protected from WD-induced anxiety. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,437 genes significantly regulated by Tas1r3 deficiency. In addition, bioinformatic analysis revealed that CREB-mediated maintenance of neuronal regeneration, which can prevent the development of anxiety, was enhanced in WD-fed Tas1r3-/- mice compared to WD-fed WT mice. In addition, in vitro studies further confirmed that Tas1r3 knockdown prevented suppression of CREB caused by high levels of glucose, fructose, and palmitic acid in adult hypothalamic neuronal cells. These results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of the WD on anxiety.
2023-08-05 | GSE216063 | GEO
Project description:Purpose: Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles and inflammatory cell infiltration in the inflamed bowel tissues of WD-fed Tas1r3-deficient mice. Methods: We carried out RNA-Seq of ileum tissue of wild-type (WT) and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed a normal diet (ND) or western diet (WD) for 10 weeks using Ion Proton System. Raw RNA-seq reads were split into individual samples based on barcodes and quality controlled using the FASTQC tool. The reads were analyzed with Partek Flow software (Partek, St. Louis, MI, USA) (http://www.partek.com/partekgs). The sequence reads that passed quality filters were analyzed at the transcript isoform level. Results: We confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Consistent with little or no phenotypic change in the ND group, the gene expression profiles from the ND-fed Tas1r3−/− and WT mice were similar, whereas the ileal transcriptome profiles from the WD-fed Tas1r3−/− mice were readily distinguishable from those of WD-fed WT mice. Inflammatory cytokines such as Tnfα and Il1b were highly expressed in WD-fed WT mice, whereas Pparg, Tjp3, and Defa27 were highly expressed in WD-fed Tas1r3−/− mice. Importantly, we confirmed that the absence of TAS1R3 caused a significant reduction in the inflammatory response-related signaling pathway; GSEA plots also revealed that the mTOR signaling pathway was greatly suppressed. Most notably, the PPAR signaling pathway was significantly affected by TAS1R3 absence. GSEA confirmed that genes associated with the PPAR signaling pathway were significantly enriched in the set of DEGs between Tas1r3−/− and WT mice in the WD groups. Conclusion: Our data suggest that, due to its suppressive action on mTOR, TAS1R3 might function as an important regulator of the PPAR-γ signaling pathway in the intestinal tract.
2023-04-19 | GSE190059 | GEO
Project description:Effect of deficiency of TAS1R3 on testicular gene expression in male mice
| PRJNA942623 | ENA
Project description:The taste receptor TAS1R3 regulates small intestinal tuft cell homeostasis
| PRJNA589590 | ENA
Project description:Taste stem/progenitor cells from the mouse posterior tongue have been recently used to generate taste bud organoids. However, the inaccessible location of the taste receptor cells is observed in conventional organoids. Here, we established a suspension culture method for fine tuning of taste bud organoid by apicobasal polarity alteration to form the accessible localization of taste receptor cells in organoid. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells on the outer region of taste bud organoids enabled the direct application of calcium imaging for evaluating the taste response. Moreover, suspension-cultured organoids could be genetically altered using gene editing methods. Suspension-cultured taste bud organoid harmoniously integrated with the recipient lingual epithelium; maintained the taste receptor cells and gustatory innervation capacity. Thus, we propose that suspension-cultured organoids may provide efficient model for taste research including taste bud development, regeneration and transplantation
2021-12-25 | GSE191169 | GEO
Project description:Serine protease inhibitors have therapeutic potential in a variety of pathogenic processes, ranging from thrombosis, altered immune response to liver cirrhosis. To investigate the physiological effects of protein C inhibitor (PCI, serpinA5) this gene was inactivated in a mouse model with the resulting phenotype of male infertility. In the actual report 2D-DIGE analysis was utilized to investigate the molecular mechanisms for PCI in male reproduction. Comparing the testes proteome of three PCI knockout-mice with the three wild-types- demonstrated similar pattern with the exception of a massive upregulation of prostaglandin reductase 1 (10-fold; P < 0.002) and complete shifts in the molecular weights of serpinA1C and serpinA3K. All these PCI-dependent proteome changes were immunologically verified. Unbiased proteome analysis indicated that the inactivation of serpinA5 strongly influenced both the protein species pattern of other A-clade serpins as well as the prostaglandin metabolism in the testes.
2015-12-07 | PXD002944 | Pride
Project description:Serine protease is considered a relative upstream regulator in the physiological processes including male reproduction. Transmembrane serine protease 12 (TMPRSS12) has been shown to regulate sperm motility and uterotubal junction migration in mice, but its role in the testis remains unknown.In this study, we confirmed the important role of TMPRSS12 in spermatogenesis. To further investigate the mechanism of TMPRSS12 in male reproduction, we used 2-D electrophoresis combined with Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry(MALDI-TOF/TOF) to construct differential protein expression profiles of testes in Tmprss12-/- and WT mice. A total of 64 spots with 2-fold or more differential expression between two groups were identified using MALDI-TOF/TOF. As a result, 54 unique proteins were identified successfully, including 39 proteins with decreased expression and 15 proteins with increased expression in Tmprss12-/- mice.
2022-05-20 | PXD028014 | Pride