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

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. [Display omitted] • We identify cell-type-specific aging-related genes in the olfactory epithelium • Aging leads to the presence of activated horizontal basal cells • Egr1 and Cebpb are core regulatory factors in the transcriptional network • Aging alters expression levels and frequencies of specific olfactory receptors Li et al. perform a single-cell transcriptomic analysis of young and aged mouse olfactory epithelium and identify aging-related genes, including Egr1. They find the presence of activated HBCs in the aged olfactory epithelium and show specific olfactory receptors with altered expression levels and frequencies by aging. [ABSTRACT FROM AUTHOR]