Tamoxifen triggers a transcriptional switch from proliferation to differentiation in the circumvallate taste epithelium in mice

TL;DR

Tamoxifen causes taste cells in mice to shift from growing to maturing, which could affect taste research using this drug.

Contribution

The study reveals tamoxifen's direct effect on taste epithelium by inducing a transcriptional shift from proliferation to differentiation.

Findings

Tamoxifen reduces cell supply to taste buds in a dose-dependent manner.

Tamoxifen downregulates cell cycle genes and upregulates differentiation-related genes in the circumvallate epithelium.

Transcription factors like Pou2f3, Ascl1, and Nkx2-2 are induced, promoting differentiation of all taste cell types.

Abstract

The tamoxifen-inducible Cre-loxP system is an indispensable experimental tool in life sciences for inducing spatiotemporally controlled genetic recombination in the target tissues of living animals. The use of this technology is expected to increase in taste research. However, the direct effects of tamoxifen on taste buds remain largely unexplored. Here, we demonstrate that tamoxifen reduces cell supply to the taste buds in a dose-dependent manner. RNA sequencing of the circumvallate epithelium revealed that tamoxifen induced a transcriptional shift from proliferation to differentiation. The genes regulating the cell cycle were downregulated, whereas genes promoting the differentiation of epithelial cells and keratinocytes were upregulated. Within taste buds, Shh was downregulated in immature precursor cells, whereas cell type-specific genes were broadly upregulated in mature taste bud cells. Notably, transcription factors driving taste cell type differentiation, such as Pou2f3, Ascl1, and Nkx2-2, were induced, suggesting that tamoxifen activates transcription to promote the differentiation of all cell types in taste buds, rather than activating particular signaling pathways in specific cell types. These findings indicate that tamoxifen rapidly triggers a transcriptional switch from proliferation to differentiation in the circumvallate taste epithelium, highlighting a potential confounding effect in taste research that employs tamoxifen administration.

The online version contains supplementary material available at 10.1038/s41598-025-32701-8.

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