ISRIB promotes alveolar epithelial differentiation after pneumonectomy. (A) Schematic of the experiment design. Young adult SftpcERCre × zsGreen mice (3 to 5 mo) received 10 mg of tamoxifen via oral gavage on 2 sequential days 14 d prior to pneumonectomy (PNX). Mice were treated with ISRIB 25 mg/kg intraperitoneally or vehicle 1 d after pneumonectomy, analysis performed on day 7 after pneumonectomy on postcaval lobe. (B) Representative flow cytometry plots, from SftpcERCre × zsGreen mice, gated on CD45–EpCAM+MHC II+GFP+ cells. (C) Quantification of GFP+PDPN– AT cells and GFP+PDPN+ AT1 cells in vehicle- and ISRIB-treated mice. Data are shown as mean ± SEM, 3 to 8 mice per group. One-way ANOVA with Tukey–Kramer test for multiple comparison, *P < 0.05. (D) Representative images of lung tissue (postcaval lobe) from young adult mice 7 d after pneumonectomy and a single dose of ISRIB or vehicle at day 1 postpneumonectomy. The arrows indicate GFP+PDPN+ AT1 cells derived from GFP+ AT2 cells. (Scale bar, 100 μm.)