Single-cell transcriptomic atlas of taste papilla aging.

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.