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A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte

机译：气道上皮细胞单细胞图谱显示富含CFTR的肺离子细胞

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摘要

The functions of epithelial tissues are dictated by the types, abundance and distribution of the differentiated cells they contain. Attempts to restore tissue function after damage require knowledge of how physiological tasks are distributed among cell types, and how cell states vary between homeostasis, injury-repair and disease. In the conducting airway, a heterogeneous basal cell population gives rise to specialized luminal cells that perform mucociliary clearance(1). Here we perform single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behaviour in homeostasis and regeneration. Our analysis reveals cell states that represent known and novel cell populations, delineates their heterogeneity and identifies distinct differentiation trajectories during homeostasis and tissue repair. Finally, we identified a novel, rare cell type that we call the 'pulmonary ionocyte', which co-expresses FOXI1, multiple subunits of the vacuolar-type H+-ATPase (V-ATPase) and CFTR, the gene that is mutated in cystic fibrosis. Using immunofluorescence, modulation of signalling pathways and electrophysiology, we show that Notch signalling is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium.
机译：上皮组织的功能取决于它们所包含的分化细胞的类型，丰度和分布。试图在损伤后恢复组织功能需要了解如何在细胞类型之间分配生理任务，以及在稳态，损伤修复和疾病之间细胞状态如何变化。在传导气道中，异质基底细胞群会产生执行黏膜纤毛清除作用的特殊腔细胞（1）。在这里，我们对人支气管上皮细胞和小鼠气管上皮细胞进行单细胞分析，以获得传导气道中细胞类型及其在体内稳态和再生中的行为的全面普查。我们的分析揭示了代表已知和新型细胞群体的细胞状态，描绘了它们的异质性，并在稳态和组织修复过程中确定了不同的分化轨迹。最后，我们确定了一种新型的罕见细胞类型，我们称之为“肺离子细胞”，它共表达FOXI1，液泡型H + -ATPase（V-ATPase）和CFTR的多个亚基，该基因在囊性细胞中突变纤维化。使用免疫荧光，信号通路和电生理调节，我们表明Notch信号是必要的，并且FOXI1表达足以驱动肺离子细胞的产生，并且肺离子细胞是传导性气道上皮中CFTR活性的主要来源。

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  • 来源
    《Nature》 |2018年第7718期|377-381|共5页
  • 作者

    Plasschaert Lindsey W.; Zilionis Rapolas; Choo-Wing Rayman; Savova Virginia; Knehr Judith; Roma Guglielmo; Klein Allon M.; Jaffe Aron B.;

  • 作者单位

    Novartis Inst BioMed Res, Chem Biol & Therapeut, Cambridge, MA 02139 USA;

    Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;

    Novartis Inst BioMed Res, Chem Biol & Therapeut, Cambridge, MA 02139 USA;

    Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;

    Novartis Inst BioMed Res, Chem Biol & Therapeut, Basel, Switzerland;

    Novartis Inst BioMed Res, Chem Biol & Therapeut, Basel, Switzerland;

    Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;

    Novartis Inst BioMed Res, Chem Biol & Therapeut, Cambridge, MA 02139 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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