舌头上的味蕾包含嗜甜、嗜酸、咸味、鲜味和苦味受体细胞（TRCs），它们能够检测出这些刺激。与非味觉舌上皮一样，TRCs源于基底角质细胞，其中许多细胞表达转录因子SOX2。基因系谱追踪显示SOX2+的舌本体祖细胞能够分化为小鼠后圆囊味蕾（CVP）中的味觉和非味觉舌上皮。然而，CVP表皮细胞中SOX2的表达存在差异，这表明它们的祖细胞潜力可能有所不同。通过转录组分析和器官体技术，我们发现SOX2表达水平较高的细胞是能够产生包含TRCs和舌上皮的器官体的味觉能力祖细胞，反之，则是由SOX2表达水平较低的细胞衍生的仅由非味觉细胞组成的器官体。在成年小鼠中，Hedgehog和WNT/β-catenin对于味觉稳态至关重要，然而，在器官体中操纵Hedgehog信号对TRC分化或祖细胞增殖没有影响。相反，在由SOX2+表达水平较高的祖细胞派生的器官体中，WNT/β-catenin促进体外TRC分化而在SOX2+表达水平较低的祖细胞中则无此现象。© 2023年。The Company of Biologists Ltd.出版。

Taste buds on the tongue contain 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 that 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 epithelial cells, suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show that cells expressing SOX2 at higher levels are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium. Conversely, organoids derived from progenitors that express SOX2 at lower levels are composed entirely of non-taste cells. Hedgehog and WNT/β-catenin are required for taste homeostasis in adult mice. However, manipulation of hedgehog signaling in organoids has no impact on TRC differentiation or progenitor proliferation. By contrast, WNT/β-catenin promotes TRC differentiation in vitro in organoids derived from higher but not low SOX2+ expressing progenitors.© 2023. Published by The Company of Biologists Ltd.