A single-cell transcriptomic census of mammalian olfactory epithelium aging

IF 10.7 1区生物学 Q1 CELL BIOLOGY

Developmental cell Pub Date : 2024-08-21 DOI:10.1016/j.devcel.2024.07.020

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

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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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哺乳动物嗅上皮细胞老化的单细胞转录组普查

哺乳动物的嗅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，我们对年轻和衰老的小鼠嗅上皮细胞（OE）进行了单细胞RNA测序（scRNA-seq）分析，在21种细胞类型中鉴定出了与衰老相关的差异表达基因（DEGs）。衰老导致OE中出现活化的水平基底细胞（HBCs），并促进了HBCs与中性粒细胞之间的细胞相互作用。衰老增强了Egr1和Fos在从多能祖细胞分化而来的寄生细胞中的表达，而Bcl11b则在衰老OE的感觉神经元平衡过程中下调。Egr1和Cebpb是预测OE转录网络的核心调控因子。在老化OE器官组织中过表达Egr1可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。这些发现在单细胞分辨率上提供了OE衰老的细胞和分子框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental cell 生物-发育生物学

CiteScore

18.90

自引率

1.70%

发文量

203

审稿时长

3-6 weeks

期刊介绍： Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.