A Single-Cell Atlas of the Human Healthy Airways
A Single-Cell Atlas of the Human Healthy Airways
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DOI：
10.1164/rccm.201911-2199oc
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发表时间：
2020-12-15
影响因子：
24.7
通讯作者：
Barbry, Pascal
中科院分区：
文献类型：
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作者：
Deprez, Marie;Zaragosi, Laure-Emmanuelle;Barbry, Pascal
基本原理：呼吸道构成了一条基于独特细胞生态系统的精细防线。
目的：我们旨在通过单细胞RNA分析来研究沿气道的细胞群体分布和转录变化。
方法：我们通过单细胞RNA分析探索了10名健康活体志愿者的人气道上皮细胞的异质性。从鼻子到气道树的第12级分支的35个不同位置共收集了77969个细胞。
测量和主要结果：所得图谱由高比例的上皮细胞（89.1%）以及免疫细胞（6.2%）和基质细胞（4.7%）组成，这些细胞在气道的不同区域具有不同的细胞比例。它揭示了来自鼻子（MUC4、PI3、SIX3）和气管支气管（SCGB1A1、TFF3）气道的相同细胞类型（基底上层细胞、分泌细胞和多纤毛细胞）之间的差异基因表达。相比之下，细胞类型特异性基因表达在所有气管支气管样本中是稳定的。我们的图谱改进了对离子细胞、肺神经内分泌细胞和刷细胞的描述，并确定了一个相关的NREP阳性细胞群体。我们还报告了KRT13与分裂细胞的关联，这些分裂细胞让人联想到先前描述的小鼠“丘状”细胞以及与表达SCEL和SPRR1A/B的鳞状细胞的关联。
结论：对健康气道中单个细胞群的有力表征为未来的研究建立了有价值的资源。对从鼻上皮到气道连续分支存在的连续体的精确描述以及这些区域稳定的基因表达谱更好地定义了可以开发人类呼吸道疾病相关气管支气管替代物的条件。
Rationale: The respiratory tract constitutes an elaborate line of defense that is based on a unique cellular ecosystem.Objectives: We aimed to investigate cell population distributions and transcriptional changes along the airways by using single-cell RNA profiling.Methods: We have explored the cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. A total of 77,969 cells were collected at 35 distinct locations, from the nose to the 12th division of the airway tree.Measurements and Main Results: The resulting atlas is composed of a high percentage of epithelial cells (89.1%) but also immune (6.2%) and stromal (4.7%) cells with distinct cellular proportions in different regions of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type-specific gene expression is stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuroendocrine cells, and brush cells and identifies a related population of NREP-positive cells. We also report the association of KRT13 with dividing cells that are reminiscent of previously described mouse "hillock" cells and with squamous cells expressing SCEL and SPRR1A/B.Conclusions: Robust characterization of a single-cell cohort in healthy airways establishes a valuable resource for future investigations. The precise description of the continuum existing from the nasal epithelium to successive divisions of the airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.