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.