Fig. 10. Embryonic deletion of p21 or treatment with a senolytic cocktail during the saccular stage disrupts lung development.

a–f Lungs from p21 knockout mice and WT mice were collected at pnd4, pnd7 or pnd14 under normoxia. a, b Lung SA-β-gal activity and lamin b1 staining were performed, and cells positive for SA-β-gal or without nuclear lamin b1 were counted and normalized to total numbers of nuclei. c–f H&E staining was performed in the lung at pnd7 and pnd14 to measure number of alveoli and secondary crests, Lm and RAC. g Immunofluorescence of vWF was performed to detect the number of vWF positive blood vessels in the lung. h–o Lungs from C57BL/6 J mice were collected at pnd4, pnd7 or pnd14 under normoxia when they were treated Que/Das (2.5 mg/kg) at pnd1 and pnd3. h–j SA-β-gal activity, lamin b1 expression, and p21 mRNA was measured in the lung at pnd4. Cells positive for SA-β-gal or without nuclear lamin b1 were counted and normalized to total numbers of nuclei in the lungs. k–n H&E staining was performed in the lung at pnd7 and pnd14 to measure number of alveoli and secondary crests, Lm and RAC. o Immunofluorescence of vWF was performed to detect the number of vWF positive blood vessels in the lung at pnd7 and pnd14. p Schematic figure showing timing of senescence in mediating postnatal lung development and hyperoxic lung injury. Data are expressed as mean ± SEM. N = 6–8 mice per group. Source data are provided as a Source Data file. One-way ANOVA followed by Tukey post-test was used for multiple comparisons (a–g, k–o), while t-test was used in panels (h–j). *P < 0.05, **P < 0.01, ***P < 0.001 vs corresponding WT (a–g) or vehicle (h–o) group.