Fig. 5: TRβ activation promotes M-AT2 cells differentiation into AT1 cells.

a RNA-velocity analysis of AT2 cells, Krt8⁺ cells, and AT1 cells in scRNA-seq data. The arrows indicate the predicted lineage trajectories. b Heatmap showing the average FPKM value of AT1 cell genes per group in mouse lung bulk RNA-seq (same as Fig. 3c, n = 3). c, d Protein and mRNA levels of AT1 cell markers in lung homogenates (n = 3), same as Fig. 3. e AT2-lineage tracing mice were used to detect AT2 differentiation with a time-lapse. f Representative IF images from lung cryosections stained with antibodies against KRT8 and PDPN. Arrows point to KRT8⁺ cells, arrowheads indicate AT1 from lineage-labeled AT2 differentiation, and unfilled arrows point to KRT8⁺ lineage-labeled cells with basaloid morphology (n = 3). Scale bars, 50 μm. g Quantification of indicated cells in (f) (left, n = 15; right, BLM n = 10, BLM + GC-1 n = 11). h The percentage of KT8⁺tdT⁺ cells were tested by flow cytometry at d14 after lung digestion (n = 3). i, j Immunoblotting and qPCR analysis of AT1 marker genes after GC-1 treatment with dose gradient in A549 (j, n = 3) and MLE12. The value of n indicates biologically independent samples (d, h, j). Data of different sections from three biologically independent mice (g). Similar results were repeated in two biologically independent experiments. Significant differences were obtained using one-way ANOVA with Turkey’s multiple comparison tests. Error bars, SEM.