Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent re...Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago,the mechanisms underlying these phenomena(e.g.,heterogenous cellular responses to nerve injury and the signaling pathways involved)remain poorly understood.Here,using mouse genetics,nerve injury models,pharmacologic manipulation,and taste bud organoid models,we identify a specific subpopulation of taste cells,predominantly c-Kit-expressing sweet cells,that exhibit superior resistance to nerve injury.We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2,subsequently attenuating the re-emergence of other type II cells by post-operation week 4.In taste bud organoids,c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib,while other taste cell types showed the opposite behavior.We also observed a distinct population of residual taste cells that acquired stem-like properties,generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling.Together,our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government(Ministry of Science and ICT,RS-2023-00208193 to Y.T.J.)by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare(RS-2024-00403511 to D.-H.K.)by a Korea University grant(K2117151 to Y.T.J.)。
文摘Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago,the mechanisms underlying these phenomena(e.g.,heterogenous cellular responses to nerve injury and the signaling pathways involved)remain poorly understood.Here,using mouse genetics,nerve injury models,pharmacologic manipulation,and taste bud organoid models,we identify a specific subpopulation of taste cells,predominantly c-Kit-expressing sweet cells,that exhibit superior resistance to nerve injury.We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2,subsequently attenuating the re-emergence of other type II cells by post-operation week 4.In taste bud organoids,c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib,while other taste cell types showed the opposite behavior.We also observed a distinct population of residual taste cells that acquired stem-like properties,generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling.Together,our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.
