A single-cell transcriptomic census of mammalian olfactory epithelium aging

Area of Science:

• Neuroscience
• Gerontology
• Molecular Biology

Background:

• The mammalian olfactory epithelium (OE) possesses lifelong self-renewal capacity.
• Olfactory dysfunction is a common consequence of aging.
• Understanding OE aging mechanisms is crucial for addressing olfactory decline.

Purpose of the Study:

• To investigate the cellular and molecular changes in the aged murine OE using single-cell RNA sequencing.
• To identify aging-related differentially expressed genes (DEGs) and their functional implications.
• To explore potential therapeutic targets for age-related olfactory dysfunction.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of young and aged murine OE.
• Differential gene expression analysis across 21 cell types.
• Analysis of cellular interactions and regulatory networks.
• Validation in aged OE organoids.

Main Results:

• Aging activates horizontal basal cells (HBCs) and increases HBC-neutrophil interactions.
• Sustentacular cell differentiation shows enhanced Egr1 and Fos expression, while Bcl11b is downregulated in aged OE.
• Egr1 and Cebpb identified as core regulatory factors.
• Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation.
• Altered expression levels and frequencies of olfactory receptors were observed in aged OE.

Conclusions:

• Aging significantly remodels the cellular and molecular landscape of the OE at single-cell resolution.
• Specific genes like Egr1 play critical roles in OE aging and neuronal homeostasis.
• Egr1 shows potential as a therapeutic target to improve olfactory function in aging individuals.