Fig. 1

Histology and in vitro CFE of human samples with the ALDH2/ALDH2 or ALDH2/ALDH2*2 heterozygous alleles. Bronchial sections from all individuals were stained with H&E and were immunostained for basal, goblet, and ciliated cell markers using antibodies against K5, MUC5AC, and β-tubulin, respectively. a-f show representative images for: normal epithelial lining (a, b) goblet cell hyperplasia c, d and basal cell hyperplasia (e, f). Bronchial and lung epithelial cells isolated from ALDH2/ALDH2 and ALDH2/ALDH2*2 heterozygous samples were cultured in the in vitro 3D- stem cell colony forming assay. Representative images are shown for the bronchial colonies (g, h) and lung colonies (i, j) from the ALDH2/ALDH2 and ALDH2/ALDH2*2 heterozygous samples, respectively. k, l show representative images for the inducing effect of ALDH2 activation by Alda-1 treatment on the bronchial CFE (compare to g and h). CFE of the primary and clonally passaged cells were calculated for all the samples examined (m-o). The effect of ALDH2 activation on CFE was calculated for each sample from parallel-treated culture wells. The percentage of increase in CFE in comparison to the untreated wells is shown (p, q). ALDH2: ALDH2/ALDH2, ALDH2*2: ALDH2/ALDH2*2, Bron: bronchial, Col: colonies. Scale bars: (a-f) 20 μm; (g-l) 500 μm. b, d, and f: Nuclei were stained with DAPI (blue)