Fig. 4: Airway basal cells participate in alveolar regeneration in SARS-CoV-2 infected hamsters.

a Proposed trajectory of airway basal cells towards alveolar cells. Upon severe alveolar damage, rare ΔNp63⁺CK14⁺ and frequent CK14⁺ basal cells differentiate into alveolar pneumocytes type 2 (AT2) and/or alveolar differentiation intermediate (ADI) cells, particularly at 6 dpi. At 14 dpi, CK14⁺ basal cells differentiate into secretoglobin 1A1⁺ (SCGB1A1) club cells within peribronchiolar alveolar proliferates. b, c Quantification of CK14⁺ basal cells (b) and SCGB1A1⁺ club cells (c) within intrapulmonary airways, total alveoli, non-affected alveoli, and affected alveoli. Pictures of immunolabeled cells (brown signal) in the bronchioles and peribronchiolar proliferates in mock and SARS-CoV-2 infected hamsters at 6 and 14 days post infection (dpi), taken from the same ___location for both stains. d Double immunofluorescence for CK14 (green) and pro-surfactant protein C (proSP-C, red) in a peribronchiolar proliferation area in a SARS-CoV-2 infected hamster at 6 dpi. Arrowhead: proSP-C⁺ AT2 cell. Arrows: double-labeled airway progenitors differentiating into proSP-C⁺ AT2 cells. e Double immunofluorescence for CK14 (red) and CK8 (green) in a peribronchiolar proliferation area in a SARS-CoV-2 infected hamster at 6 dpi. The transition from CK14⁺ airway basal cells forming a pod (white arrowhead) to CK14⁺CK8⁺ cells differentiating into elongated ADI cells (open arrowheads) and CK14^-CK8⁺, elongated ADI cells (arrows). f Double immunofluorescence for CK14 (green) and SCGB1A1 (red) in a peribronchiolar proliferation area in a SARS-CoV-2 infected hamster at 14 dpi. Transition from CK14⁺ airway basal cells (arrowhead) to CK14⁺SCGB1A1⁺ club cells (arrows) is shown. Quantification data are shown as box and whisker plots. The bounds of the box plot indicate the 25th and 75th percentiles, the bar indicates medians, and the whiskers indicate minima and maxima. Dots indicate individual values. Statistical analysis was performed by two-tailed Mann–Whitney U test. For multiple comparisons between time points, a Benjamini–Hochberg correction was applied. P- and q values ≤ 0.05 were considered significant. N = 10 animals/group for mock and SARS-CoV-2 respectively. Source data are provided as a Source Data file. Scale bars: 100 µm (c, d), 50 µm (overview in d–f), 25 µm (high magnification in d–f).