A single-cell transcriptomic census of mammalian olfactory epithelium aging.

Weihao Li, Tingting Wu, Kesen Zhu, Guangyi Ba, Jinxia Liu, Ping Zhou, Shengjv Li, Li Wang, Huanhai Liu, Wenwen Ren, Hongmeng Yu, Yiqun Yu

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Olfactory Disorder Diagnosis and Treatment Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China. · pubmed

Paper

Abstract

Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.

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Research summary

The paper investigates the cellular and molecular changes in the olfactory epithelium associated with aging, which is directly relevant to understanding the biological mechanisms of aging. While it provides valuable insights into the aging process at a single-cell level, the findings appear to be more descriptive and incremental rather than groundbreaking. The identification of differentially expressed genes and cellular interactions contributes to the field but does not propose a novel approach to mitigate aging or extend lifespan.

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