Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway
Fig 7
Human lung BSCs are the putative cells of origin of lung squamous cell carcinoma.
(A) Representative histogram of intracellular DAPI staining of BSCs and AT2 cells isolated from a 56-y-old male exsmoker patient. Gates indicate 2N, 4N, and polyploid cells. (B) Proportion of polyploidy cells in the BSC and AT2 subsets. n = 3 patients (a 69-y-old female exsmoker, a 56-y-old male exsmoker, and a 70-y-old female exsmoker). Paired t test. (C) Boxplots of human lung BSC expression scores by lung tumour subtypes (ADC, adenocarcinoma; SCLC, small cell lung cancer; SqCC, squamous cell carcinoma). The width of each box indicates the sample size. (D) Barcode plot showing strong correlation of the human lung BSC expression signature with that of SqCCs (ROAST p = 0.0001). Genes are sorted left to right from most up- to most down-regulated in SqCC relative to all other cancer subtypes. Positive BSC signature genes are marked with vertical red bars, and negative signatures genes are marked in blue. Variable-height bars show log-fold-change strength for each signature gene. (E) Fold changes in the expression of genes frequently altered in lung SqCC between human BSCs and other human lung epithelial cell types. n = 3 patients (a 64-y-old male exsmoker, an 83-y-old male exsmoker, and a 53-y-old male current smoker). (F) Violin plots showing expression levels of PRKDC and XRCC6 in normal lung tissue (n = 54), lung ADCs (n = 125), and lung SqCCs (n = 224) from The Cancer Genome Atlas (TCGA). Violin bodies show log2 counts per million (log CPM) expression values as smoothed densities. All pairwise p-values are <10−6 by moderated t tests. (G) Proportion of genome altered versus PRKDC and XRCC6 expression levels in TCGA lung SqCC data (n = 179). Expression levels are split into quartiles. Significance was determined by Student’s t tests. The underlying data for panels A, B, C, D, E, and G can be found in the S1 Data file.