Inducible POU2F3 expression in human intestinal organoids as a model of human tuft cells

We genetically engineered human intestinal organoids (HIOs) to express POU2F3, a transcription factor that drives tuft cell specification, and created an HIO that is approximately 40% tuft cell composition. Results: Human tuft cells generated in vitro express known tuft cell-specific transcripts (AVIL, TRPM5, ALOX5, PLCG2) as well as exhibit characteristics in vivo tuft morphology. Organoids with tuft cells exhibit transcriptional signatures that suggest WNT signaling and the presence of non-motile cilium.

The tuft cells were infectable with human rotavirus, which has recently been shown to be a new target of rotavirus infection in the intestine. Conclusions: The expression of POU2F3 in HIOs results in a novel model system for functional studies of human intestinal tuft cells.