Ontogeny and Biology of Human Small Airway Epithelial Club Cells.
| Publication Type | Academic Article |
| Authors | Zuo W, Shenoy S, Li S, O'Beirne S, Strulovici-Barel Y, Leopold P, Wang G, Staudt M, Walters M, Mason C, Kaner R, Mezey J, Crystal R |
| Journal | Am J Respir Crit Care Med |
| Volume | 198 |
| Issue | 11 |
| Pagination | 1375-1388 |
| Date Published | 12/01/2018 |
| ISSN | 1535-4970 |
| Keywords | Bronchi, Epithelial Cells, Gene Expression Profiling, Respiratory Mucosa, Transcriptome |
| Abstract | RATIONALE: Little is known about human club cells, dome-shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small airways (at least sixth-generation bronchi). OBJECTIVES: To define the ontogeny and biology of the human small airway epithelium club cell. METHODS: The small airway epithelium was sampled from the normal human lung by bronchoscopy and brushing. Single-cell transcriptome analysis and air-liquid interface culture were used to assess club cell ontogeny and biology. MEASUREMENTS AND MAIN RESULTS: We identified the club cell population by unbiased clustering using single-cell transcriptome sequencing. Principal component gradient analysis uncovered an ontologic link between KRT5 (keratin 5)+ basal cells and SCGB1A1 (secretoglobin family 1A member 1)+ club cells, a hypothesis verified by demonstrating in vitro that a pure population of human KRT5+ SCGB1A1- small airway epithelial basal cells differentiate into SCGB1A1+KRT5- club cells on air-liquid interface culture. Using SCGB1A1 as the marker of club cells, the single-cell analysis identified novel roles for these cells in host defense, xenobiotic metabolism, antiprotease, physical barrier function, monogenic lung disorders, and receptors for human viruses. CONCLUSIONS: These observations provide novel insights into the molecular phenotype and biologic functions of the human club cell population and identify basal cells as the human progenitor cells for club cells. |
| DOI | 10.1164/rccm.201710-2107OC |
| PubMed ID | 29874100 |
| PubMed Central ID | PMC6290945 |