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味蕾衰老的单细胞转录组图谱

Single-cell transcriptomic atlas of taste papilla aging.

作者信息

Ren Wenwen, Li Weihao, Cha Xudong, Wang Shenglei, Cai Boyu, Wang Tianyu, Li Fengzhen, Li Tengfei, Xie Yingqi, Xu Zengyi, Wang Zhe, Liu Huanhai, Yu Yiqun

机构信息

Department of Otolaryngology, The Second Affiliated Hospital of the Naval Medical University (Shanghai Changzheng Hospital), Shanghai, China.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

出版信息

Aging Cell. 2024 Dec;23(12):e14308. doi: 10.1111/acel.14308. Epub 2024 Aug 21.

Abstract

Taste perception is one of the important senses in mammals. Taste dysfunction causes significant inconvenience in daily life, leading to subhealth and even life-threatening condition. Aging is a major cause to taste dysfunction, while the underlying feature related to gustatory aging is still not known. Using single-cell RNA Sequencing, differentially expressed genes between aged and young taste papillae are identified, including upregulated mt-Nd4l and Xist, as well as downregulated Hsp90ab1 and Tmem59. In the Tmem59 circumvallate papillae (CVP), taste mature cell generation is impaired by reduction in the numbers of PLCβ2 and Car4 cells, as well as decreases in expression levels of taste transduction genes. Tmem59 mice showed deficits in sensitivities to tastants. Through screening by GenAge and DisGeNET databases, aging-dependent genes and oral disease-associated genes are identified in taste papillae. In the CVP, aging promotes intercellular communication reciprocally between (cycling) basal cell and mature taste cell by upregulated Crlf1/Lifr and Adam15/Itga5 signaling. By transcriptional network analysis, ribosome proteins, Anxa1, Prdx5, and Hmgb1/2 are identified as transcriptional hubs in the aged taste papillae. Chronological aging-associated transcriptional changes throughout taste cell maturation are revealed. Aged taste papillae contain more Muc5b cells that are not localized in gustatory gland. Collectively, this study shows molecular and cellular features associated with taste papilla aging.

摘要

味觉感知是哺乳动物重要的感官之一。味觉功能障碍会给日常生活带来极大不便,导致亚健康甚至危及生命的状况。衰老 是味觉功能障碍的主要原因,而与味觉衰老相关的潜在特征仍不明确。通过单细胞RNA测序,确定了老年和年轻味乳头之间的差异表达基因,包括上调的mt-Nd4l和Xist,以及下调的Hsp90ab1和Tmem59。在Tmem59轮廓乳头(CVP)中,PLCβ2和Car4细胞数量的减少以及味觉转导基因表达水平的降低会损害味觉成熟细胞的生成。Tmem59小鼠对味觉刺激物的敏感性存在缺陷。通过GenAge和DisGeNET数据库筛选,在味乳头中鉴定出衰老相关基因和口腔疾病相关基因。在CVP中,衰老通过上调Crlf1/Lifr和Adam15/Itga5信号通路,促进(循环)基底细胞和成熟味觉细胞之间的相互细胞间通讯。通过转录网络分析,核糖体蛋白、Anxa1、Prdx5和Hmgb1/2被确定为老年味乳头中的转录枢纽。揭示了味觉细胞成熟过程中与时间顺序衰老相关的转录变化。老年味乳头含有更多不位于味觉腺的Muc5b细胞。总的来说,这项研究展示了与味乳头衰老相关的分子和细胞特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c69/11634696/b55980439ead/ACEL-23-e14308-g006.jpg

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