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哺乳动物嗅觉表皮老化的单细胞转录基因普查

Weihao Li¹, Tingting Wu², Kesen Zhu²

¹ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Olfactory Disorder Diagnosis and Treatment Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.

Developmental cell

|August 22, 2024

概括

衰老会通过改变基因表达和细胞相互作用来损害嗅觉上皮质. 这项研究揭示了关键的分子变化,并确定了Egr1作为恢复老年小鼠嗅觉功能的潜在目标.

科学领域:

神经科学是一个神经科学.
老年学是一门学科.
分子生物学分子生物学

背景情况:

哺乳动物的嗅觉上皮 (OE) 具有终身自我更新的能力.
嗅觉功能障碍是衰老的一个常见后果.
了解OE衰老机制对于解决嗅觉衰退至关重要.

研究的目的:

用单细胞RNA测序研究老鼠OE中的细胞和分子变化.
确定与衰老相关的差异表达基因 (DEGs) 及其功能影响.
探索与年龄相关的嗅觉功能障碍的潜在治疗点.

主要方法:

年轻和老年小鼠OE的单细胞RNA测序 (scRNA-seq).
在21种细胞类型中进行差异基因表达分析.
细胞相互作用和调节网络的分析.
在老化的OE有机体中进行验证.

主要成果:

衰老激活水平基底细胞 (HBCs) 并增加HBC-中性细胞相互作用.
支柱状细胞分化显示了增强的Egr1和Fos表达,而Bcl11b在老年OE中是下调的.
Egr1和Cebpb被确定为核心监管因素.
过度表达Egr1在老年OE有机体中促进了细胞增殖和神经元分化.
在老年OE中观察到嗅觉受体的表达水平和频率发生变化.

结论:

衰老显著重塑了OE在单细胞分辨率上的细胞和分子格局.
像EGR1这样的特定基因在OE衰老和神经元平衡中起着关键作用.
在老年人中,EGR1显示出作为改善嗅觉功能的治疗点的潜力.

关键词:

衰老的衰老衰老的衰老横向的基本细胞水平的细胞.嗅觉上皮质是一种嗅觉上皮质.嗅觉受体是一种嗅觉受体.嗅觉感官神经元的神经元一个单细胞RNA测序.

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