Ontogeny and Biology of Human Small Airway Epithelial Club Cells

Rationale: Little is known about human club (“Clara”) cells, dome shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small air-ways (≥6th generation bronchi). Objective: 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 was used to assess club cell ontogeny and biology. Results: We identified the club cell population by the unbiased clustering using single cell transcriptome sequencing. Principal Component Gradient analysis uncovered an ontologic link be-tween KRT5+ basal cells and SCGB1A1+ club cells, a hypothesis verified by demonstrating in vitro that a pure population of human KRT5+ SCGB1A1- small airway epithelial BC differentiate into SCGB1A1+KRT5‾ club cells on air-liquid interface culture. Using SCGB1A1 as the marker of club cells, ...