Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA, 19104, United States.
Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati Ohio, OH, 45267, United States.
Sci Rep. 2017 Jun 21;7(1):4004. doi: 10.1038/s41598-017-04099-5.
Taste cells undergo constant turnover throughout life; however, the molecular mechanisms governing taste cell generation are not well understood. Using RNA-Seq, we systematically surveyed the transcriptome landscape of taste organoids at different stages of growth. Our data show the staged expression of a variety of genes and identify multiple signaling pathways underlying taste cell differentiation and taste stem/progenitor cell proliferation. For example, transcripts of taste receptors appear only or predominantly in late-stage organoids. Prior to that, transcription factors and other signaling elements are upregulated. RNA-Seq identified a number of well-characterized signaling pathways in taste organoid cultures, such as those involving Wnt, bone morphogenetic proteins (BMPs), Notch, and Hedgehog (Hh). By pharmacological manipulation, we demonstrate that Wnt, BMPs, Notch, and Hh signaling pathways are necessary for taste cell proliferation, differentiation and cell fate determination. The temporal expression profiles displayed by taste organoids may also lead to the identification of currently unknown transducer elements underlying sour, salt, and other taste qualities, given the staged expression of taste receptor genes and taste transduction elements in cultured organoids.
味蕾细胞在整个生命过程中不断更新;然而,控制味觉细胞生成的分子机制尚不清楚。使用 RNA-Seq,我们系统地调查了不同生长阶段的味觉类器官的转录组景观。我们的数据显示了各种基因的阶段性表达,并确定了味觉细胞分化和味觉干细胞/祖细胞增殖的多种信号通路。例如,味觉受体的转录本仅或主要出现在晚期类器官中。在此之前,转录因子和其他信号元件被上调。RNA-Seq 在味觉类器官培养物中鉴定出许多特征明确的信号通路,例如涉及 Wnt、骨形态发生蛋白 (BMPs)、Notch 和 Hedgehog (Hh) 的信号通路。通过药理学处理,我们证明 Wnt、BMPs、Notch 和 Hh 信号通路对于味觉细胞的增殖、分化和细胞命运决定是必需的。鉴于味觉受体基因和味觉转导元件在培养类器官中的阶段性表达,味觉类器官显示的时间表达谱也可能导致对目前未知的酸味、咸味和其他味觉品质的转导元件的鉴定。