Chloride channels regulate differentiation and barrier functions of the mammalian airway
- University of California, San Francisco, United States
- Chan Zuckerberg Biohub, United States
- Yale University School of Medicine, United States
Abstract
The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. The molecular events required for the formation and function of the airway mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway diseases, remain unclear. In this study, we systematically characterized the developmental landscape of the mouse airway using single-cell RNA sequencing and identified remarkably conserved cellular programs operating during human fetal development. We demonstrated that in mouse, genetic inactivation of chloride channel Ano1/Tmem16a compromises airway barrier function, results in early signs of inflammation, and alters the airway cellular landscape by depleting epithelial progenitors. Mouse Ano1-/- mutants exhibited mucus obstruction and abnormal mucociliary clearance that resemble the airway defects associated with cystic fibrosis. The data reveal critical and non-redundant roles for Ano1 in organogenesis, and show that chloride channels are essential for mammalian airway formation and function.
Data availability
Sequencing reads and processed data in the format of gene-cell count tables are available from the Sequence Read Archive (SRA) (SRA accession: PRJNA548516).
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trachea developmentNCBI Bioproject, PRJNA548516.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (RO1 NS069229)
- Lily Yeh Jan
Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD089639)
- Mu He
Howard Hughes Medical Institute
- Yuh Nung Jan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edward E Morrisey, University of Pennsylvania, United States
Version history
- Received: October 27, 2019
- Accepted: April 13, 2020
- Accepted Manuscript published: April 14, 2020 (version 1)
- Version of Record published: April 24, 2020 (version 2)
Copyright
© 2020, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Chloride channels regulate differentiation and barrier functions of the mammalian airway
eLife 9:e53085.
https://doi.org/10.7554/eLife.53085
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Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.
