哺乳动物的嗅觉上皮具有终生自我更新的能力。衰老是导致嗅觉功能障碍的主要原因之一。在这里，我们对年轻和老年小鼠嗅觉上皮 (OE) 进行了单细胞 RNA 测序 (scRNA-seq) 分析，并在 21 种细​​胞类型中鉴定了与衰老相关的差异表达基因 (DEG)。衰老导致 OE 中出现激活的水平基底细胞 (HBC)，并促进 HBC 和中性粒细胞之间的细胞相互作用。衰老增强了多能祖细胞分化过程中 Egr1 和 Fos 的表达，而 Bcl11b 在衰老 OE 的感觉神经元稳态过程中表达下调。 Egr1和Cebpb是OE转录网络的预测核心调控因子。 Egr1 在老化 OE 类器官中的过度表达促进细胞增殖和神经元分化。此外，衰老改变了嗅觉受体的表达水平和频率。这些发现提供了单细胞分辨率下 OE 老化的细胞和分子框架。版权所有 © 2024 Elsevier Inc. 保留所有权利。

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.Copyright © 2024 Elsevier Inc. All rights reserved.