c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury

Abstract 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 p...

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Main Authors: Su Young Ki, Jea Hwa Jang, Dong-Hoon Kim, Yong Taek Jeong
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:International Journal of Oral Science
Online Access:https://doi.org/10.1038/s41368-025-00387-3
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author Su Young Ki
Jea Hwa Jang
Dong-Hoon Kim
Yong Taek Jeong
author_facet Su Young Ki
Jea Hwa Jang
Dong-Hoon Kim
Yong Taek Jeong
author_sort Su Young Ki
collection DOAJ
description Abstract 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.
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spelling doaj-art-c6a2cd2b3d804566a3a5aef2448c7cb32025-08-20T03:04:22ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-07-0117111510.1038/s41368-025-00387-3c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injurySu Young Ki0Jea Hwa Jang1Dong-Hoon Kim2Yong Taek Jeong3Department of Pharmacology, Korea University College of MedicineDepartment of Pharmacology, Korea University College of MedicineDepartment of Pharmacology, Korea University College of MedicineDepartment of Pharmacology, Korea University College of MedicineAbstract 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.https://doi.org/10.1038/s41368-025-00387-3
spellingShingle Su Young Ki
Jea Hwa Jang
Dong-Hoon Kim
Yong Taek Jeong
c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
International Journal of Oral Science
title c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
title_full c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
title_fullStr c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
title_full_unstemmed c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
title_short c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury
title_sort c kit signaling confers damage resistance to sweet taste cells upon nerve injury
url https://doi.org/10.1038/s41368-025-00387-3
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