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

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/beta-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/beta-catenin promotes TRC differentiation in vitro in organoids derived from higher but not low SOX2+ expressing progenitors.

Automated summary

The taste buds on the tongue consist of taste receptor cells that detect different tastes. These cells are derived from basal keratinocytes that express the transcription factor SOX2. The level of SOX2 expression determines the progenitor potential, where higher levels give rise to both taste and non-taste lingual epithelium, and lower levels give rise to only non-taste cells. The signaling pathway of WNT/beta-catenin promotes taste cell differentiation in organoids derived from high SOX2+ expressing progenitors.