Ontogeny and biology of human small airway epithelial club cells

Wu Lin Zuo, Sushila A. Shenoy, Sheng Li, Sarah L. O’Beirne, Yael Strulovici-Barel, Philip L. Leopold, Guoqing Wang, Michelle R. Staudt, Matthew S. Walters, Christopher Mason, Robert J. Kaner, Jason G. Mezey, Ronald Crystal

Research output: Contribution to journalArticle

11 Citations (Scopus)


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)1 basal cells and SCGB1A1 (secretoglobin family 1A member 1)1 club cells, a hypothesis verified by demonstrating in vitro that a pure population of human KRT51 SCGB1A12 small airway epithelial basal cells differentiate into SCGB1A11KRT52 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.

Original languageEnglish
Pages (from-to)1375-1388
Number of pages14
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number11
Publication statusPublished - 1 Dec 2018



  • Club cell
  • Principal component gradient analysis
  • Small airway epithelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Zuo, W. L., Shenoy, S. A., Li, S., O’Beirne, S. L., Strulovici-Barel, Y., Leopold, P. L., Wang, G., Staudt, M. R., Walters, M. S., Mason, C., Kaner, R. J., Mezey, J. G., & Crystal, R. (2018). Ontogeny and biology of human small airway epithelial club cells. American Journal of Respiratory and Critical Care Medicine, 198(11), 1375-1388. https://doi.org/10.1164/rccm.201710-2107OC