Dear Editor, The lung is a multi-functional organ that executes gas exchange and innate defense functions. The epithelium of respiratory tree consists of four regions from proximal to distal: trachea, bronchi, bronchiole, and alveolar regions. Multiple stem or progenitor cells are required for maintaining lung functions during normal condition and repair. The maintenance and repair of epithelium at different regions mainly depend on its resident stem or progenitor cells 1–3.

Recently, a new type of multipotent stem cells termed bronchioalveolar stem cells (BASCs) has been identified which located at the bronchioalveolar-duct junctions (BADJs) 4, 5. BASCs coexpress club cell maker secretoglobin 1a1 (Scgb1a1 or CC10) and AT2 cell maker surfactant protein C (Sftpc or SPC) 4. Using different genetic approaches, we and another group have recently demonstrated that BASCs are authentic resident stem cells that differentiate, at population level, into multiple epithelial cell lineages 6, 7. In bronchiolar-injury model, BASCs give rise to bronchiole epithelial cells including club cells and ciliated cells for repair of distal airway (unidirectional: bronchiole). In alveolar-injury model, BASCs contribute to AT2 and AT1 cells to regenerate the alveoli (uni-directional: alveoli). However, whether single BASCs have the broader bi-directional differentiation potential to regenerate both distal airway and alveoli remains unknown. In this study, using in vivo single cell clonal analysis, we identified the bi-potency of single BASCs that