Fine Tuning of Epithelial Taste Bud Organoid to Promotes Functional Recapitulation of Taste Reactivity

Abstract

Taste stem/progenitor cells in the posterior tongue have been recently used to generate taste bud organoids. However, the inaccessible location of the taste receptor cells is observed in conventional organoids. Here, we established a suspension culture method for fine tuning of taste bud organoid by apicobasal polarity alteration to form the accessible localization of taste receptor cells in organoid. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed more comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells in the outer region of taste bud organoids enabled the direct application of calcium imaging and genetic alteration by gene editing. Moreover, suspension-cultured organoids integrated harmoniously with the recipient lingual epithelium, maintained the taste receptor cells and gustatory innervation capacity after transplantation. Thus, we propose that suspension-cultured organoids may provide efficient model for taste research including taste bud development, regeneration and transplantation.