Journal
NATURE
Volume 560, Issue 7718, Pages 319-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-018-0393-7
Keywords
-
Categories
Funding
- Klarman Cell Observatory at the Broad Institute
- Manton Foundation
- HHMI
- New York Stem Cell Foundation
- NIH-NHLBI
- Ludwig Cancer Institute at Harvard
- Harvard Stem Cell Institute
- Human Frontiers Science Program
- NIH-NHLBI [1F31HL136128-01]
- NHLBI/NIH [4R00HL127181]
- Regeneration NeXT Initiative at Duke University
- NIH [P30 DK072482, R35 HL135816]
- [P01 HL051670]
- [R24 HL123482]
- [R01 DK047967]
Ask authors/readers for more resources
The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1(+) pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq', combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available