气候变化领域集成服务门户(CCPortal): R-spondin substitutes for neuronal input for taste cell regeneration in adult mice

CCPortal

DOI	10.1073/pnas.2001833118
	R-spondin substitutes for neuronal input for taste cell regeneration in adult mice
	Lin X.; Lu C.; Ohmoto M.; Choma K.; Margolskee R.F.; Matsumoto I.; Jiang P.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Taste bud cells regenerate throughout life. Taste bud maintenance depends on continuous replacement of senescent taste cells with new ones generated by adult taste stem cells. More than a century ago it was shown that taste buds degenerate after their innervating nerves are transected and that they are not restored until after reinnervation by distant gustatory ganglion neurons. Thus, neuronal input, likely via neuron-supplied factors, is required for generation of differentiated taste cells and taste bud maintenance. However, the identity of such a neuron-supplied niche factor(s) remains unclear. Here, by mining a published RNA-sequencing dataset of geniculate ganglion neurons and by in situ hybridization, we demonstrate that R-spondin-2, the ligand of Lgr5 and its homologs Lgr4/6 and stem-cell-expressed E3 ligases Rnf43/Znrf3, is expressed in nodose-petrosal and geniculate ganglion neurons. Using the glossopharyngeal nerve transection model, we show that systemic delivery of R-spondin via adenovirus can promote generation of differentiated taste cells despite denervation. Thus, exogenous R-spondin can substitute for neuronal input for taste bud cell replenishment and taste bud maintenance. Using taste organoid cultures, we show that R-spondin is required for generation of differentiated taste cells and that, in the absence of R-spondin in culture medium, taste bud cells are not generated ex vivo. Thus, we propose that R-spondin-2 may be the long-sought neuronal factor that acts on taste stem cells for maintaining taste tissue homeostasis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Lgr4/5/6; Nerve transection; R-spondin; Taste bud cells; Znrf3/Rnf43
语种	英语
scopus关键词	Lgr4 protein; Lgr5 protein; Lgr6 protein; R spondin 2 protein; R spondin protein; regulator protein; Rnf43 protein; ubiquitin protein ligase E3; unclassified drug; Znrf3 protein; adult; adult stem cell; animal tissue; Article; cell differentiation; cell regeneration; controlled study; geniculate ganglion; glossopharyngeal nerve; in situ hybridization; mouse; nodose ganglion; nodose petrosal ganglion complex; nonhuman; organoid; priority journal; real time polymerase chain reaction; single cell RNA seq; taste bud; taste bud cell
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181086
作者单位	Monell Chemical Senses Center, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Lin X.,Lu C.,Ohmoto M.,et al. R-spondin substitutes for neuronal input for taste cell regeneration in adult mice[J],2021,118(2).
APA	Lin X..,Lu C..,Ohmoto M..,Choma K..,Margolskee R.F..,...&Jiang P..(2021).R-spondin substitutes for neuronal input for taste cell regeneration in adult mice.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Lin X.,et al."R-spondin substitutes for neuronal input for taste cell regeneration in adult mice".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).