Fine-tuning of epithelial taste bud organoid to promote functional recapitulation of taste reactivity

Abstract

Taste stem/progenitor cells from posterior mouse tongues have been used to generate taste bud organoids. However, the inaccessible location of taste receptor cells is observed in conventional organoids. In this study, we established a suspension-culture method to fine-tune taste bud organoids by apicobasal polarity alteration to form the accessible localization of taste receptor cells. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed 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 enabled the direct application of calcium imaging to evaluate the taste response. Moreover, suspension-cultured organoids can be genetically altered. Suspension-cultured taste bud organoids harmoniously integrated with the recipient lingual epithelium, maintaining the taste receptor cells and gustatory innervation capacity. We propose that suspension-cultured organoids may provide an efficient model for taste research, including taste bud development, regeneration, and transplantation. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-022-04242-0.

Epithelial plasticity enhances regeneration of committed taste receptor cells following nerve injury

“…Organoid formation is a characteristic of stem/progenitor cells, and differentiated cells cannot form organoids 37 , 38 . To confirm that the differentiated cells acquired stemness by undergoing dedifferentiation, we performed a taste bud organoid formation assay as described in our previous study 39 . Dedifferentiation has been observed in various tissues during regeneration; however, subtle differences in the mechanism of dedifferentiation are observed between the taste bud and other tissues.…”

Physiology of the tongue with emphasis on taste transduction

“…In the context of taste organoids, this makes it difficult for mature taste cells to be presented with tastants in in vitro experiments. However, the work published by Adpaikar and colleagues ( 368 ) revealed that transferring organoids grown in the basement membrane, into suspension culture could reverse this apicobasal polarity, thus producing taste organoids with mature TRCs localized on its apical surface. Furthermore, they also observed that attempts to grow single cell-derived mouse taste organoids directly in suspension culture were not successful.…”

“…Furthermore, they also observed that attempts to grow single cell-derived mouse taste organoids directly in suspension culture were not successful. The mouse taste organoids first cultured in the basement membrane and then in suspension culture showed cell differentiation and renewal rates that are more similar to the native tissue, had TRCs that are more accessible to calcium imaging (thus enabling evaluation of taste transduction), and could subsequently be integrated into the host lingual epithelium without impeding its functional capacity ( 368 ).…”

The Pathogenesis of COVID-19–Related Taste Disorder and Treatments

“…Adpaikar et al developed a new approach to culturing taste bud organoids by establishing suspension-cultured organoids that maintain the correct polarity of taste buds. This advancement is significant because it enables direct measurement of taste responses, and the high accessibility of taste organs makes them an ideal model for in vitro studies (Adpaikar et al 2022). With further advances in biosensing technology, tongue organoids may develop to have biological functions, providing a platform for taste-related in vitro studies and regenerative therapies.…”