Study: Airway epithelium 7193 cells

 

A revised airway epithelial hierarchy includes CFTR expressing ionocytes

Contact: aregev@broadinstitute.org

Summary

Airways conduct gases to the distal lung and are the sites of disease in asthma and cystic fibrosis. Here, we combined single cell RNA-sequencing (scRNA-Seq) and in vivo lineage tracing to study the cellular composition and hierarchy of the murine tracheal epithelium.

 

 

We identified a new rare cell, the pulmonary ionocyte. We revised the cellular hierarchy of the epithelium and demonstrated that tuft cells, neuroendocrine cells, and ionocytes are all direct daughters of basal cells and that they are continually turned over. We further discovered a novel progenitor population that resides in “hillocks”, previously unrecognized epithelial structures. We find that club cells functionally vary based on their location within the respiratory tree, and identify disease-relevant subsets of tuft and goblet cells. Remarkably, we find that the cystic fibrosis gene, CFTR, is predominantly expressed in pulmonary ionocytes in both mouse and human. Loss of ionocytes in mouse epithelia results in the loss of Cftr expression, abnormal surface fluid, and increased mucous viscosity, all of which are altered in cystic fibrosis. By associating cell type-specific gene expression programs with key disease genes, we establish a new cellular narrative for airways disease.

Paper: Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., et al. (2018). A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature, 1–30. http://doi.org/10.1038/s41586-018-0393-7