Figure 4.

Diverse types of epithelial stem cells respond distinctly after different lung injuries. A, schematic showing the strategy for bronchiolar injury. Tam, tamoxifen. B, immunostaining for CC10, ZsGreen, and tdTomato on lung tissue sections 8 weeks after injury. Boxed regions are magnified in the right panels. White arrowheads indicate CC10⁺ club cells derived from ZsGreen⁺tdTomato⁺ BASCs. C, quantification of the ZsGreen⁺tdTomato⁺CC10⁺ club cells in each bronchiolar strand in naphthalene- or vehicle-treated lungs. Data are mean ± S.D. *, p < 0.001 by two-tailed t test. D, immunostaining for acetylated tubulin, ZsGreen, and tdTomato on lung tissue sections 8 weeks after injury. Arrowheads, acetylated tubulin⁺ ciliated cells derived from ZsGreen⁺tdTomato⁺ BASCs. E, quantification of the ZsGreen⁺tdTomato⁺acetylated tubulin⁺ ciliated cell in each bronchiolar strand. Data are mean ± S.D. *, p < 0.001 by two-tailed t test. F, cartoon showing that club cells and BASCs mainly regenerate the terminal bronchiole after bronchiolar injury. G, schematic showing the strategy for alveolar injury. H, immunostaining for SPC, ZsGreen, and tdTomato on lung tissue sections 8 weeks after injury. Arrowheads, SPC⁺ AT2 cells derived from ZsGreen⁺tdTomato⁺ BASCs. I, quantification of ZsGreen⁺tdTomato⁺SPC⁺ AT2 cells in each BADJ field in bleomycin- or vehicle-treated lungs. Data are mean ± S.D. *, p < 0.001 by two-tailed t test. J, immunostaining for T1a, ZsGreen, and tdTomato on lung tissue sections 8 weeks after injury. Arrowheads, T1a⁺ AT1 cells derived from ZsGreen⁺tdTomato⁺ BASCs. K, quantification of ZsGreen⁺tdTomato⁺T1a⁺ AT1 cells in each BADJ field. Data are mean ± S.D. *, p < 0.001 by two-tailed t test. L, cartoon showing that BASCs regenerate alveolar cells surrounding BADJs and that AT2 cells are responsible for alveolar regions away from BADJs after alveolar injury. ZsG, ZsGreen; tdT, tdTomato. Scale bars = 100 μm. Each image is representative of five individual samples.