Cellular heterogeneity and patterning strategies as revealed by upper respiratory epithelium single cell atlas

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-07 DOI:10.1016/j.isci.2025.112845

Alexander G. Foote , Xin Sun

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Abstract

The upper respiratory tract, spanning the pharyngolaryngeal to tracheobronchial regions, enables breathing, vocalization, and frontline defense against airborne insults. We generated a cellular and molecular atlas of the mouse upper respiratory epithelium from pharynx/larynx to tracheobronchial carina by combining single-cell RNA sequencing with spatial validation. Our analysis revealed 18 epithelial cell types, organized into three spatially distinct compartments: Tmprss11a+ pharyngolaryngeal, Nkx2-1+ tracheobronchial, and Dmbt1+ submucosal glands. Stratified squamous pharyngolaryngeal zones displayed extensive and region-specific Keratin codes. Within the pseudostratified tracheobronchial epithelium, diverse luminal cells, including multiple varieties of club cells, exhibit marker-expression gradients along the proximal–distal axes. Lastly, analysis of the submucosal gland epithelium —which contains various cell types, including distinctive myoepithelial cells— revealed extensive diversity both among and within its cellular populations. This spatially resolved transcriptomic atlas elucidates how epithelial identity varies along the upper respiratory axes and will guide investigations into cellular dynamics in health and disease.

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上呼吸道上皮单细胞图谱揭示的细胞异质性和模式策略

上呼吸道横跨咽部到气管支气管区域，使呼吸、发声和对空气中侮辱的前线防御成为可能。我们通过单细胞RNA测序和空间验证相结合，生成了从咽部到气管支气管隆突的小鼠上呼吸道上皮细胞和分子图谱。我们的分析揭示了18种上皮细胞类型，它们在空间上分为三个不同的区室：Tmprss11a+咽喉腺、Nkx2-1+气管支气管和Dmbt1+粘膜下腺。分层鳞状咽区显示广泛和区域特异性角蛋白编码。在假层状气管支气管上皮内，多种管腔细胞，包括多种球杆细胞，沿近端至远端轴表现出标记物表达梯度。最后，对粘膜下腺上皮（包含多种细胞类型，包括独特的肌上皮细胞）的分析揭示了其细胞群之间和内部的广泛多样性。这个空间解析的转录组图谱阐明了上皮身份如何沿着上呼吸道轴变化，并将指导健康和疾病中的细胞动力学研究。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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