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. 2022 Mar 14;41(8):e109365. doi: 10.15252/embj.2021109365

Figure 2. Sustained activation of YAP/TAZ drives the fate conversion of secretory cells into AT1 cells via DATP cell states.

Figure 2

  • A
    Experimental design for isolating Scgb1a1 lineage‐labeled cells from control and Lats1/2 dKO lungs at indicated time points post tamoxifen treatment. Isolated cells were subjected to scRNA‐seq analysis.
  • B
    Clusters of Scgb1a1 lineage‐labeled cells from 10XGenomics 3’ single‐cell RNA sequencing (scRNA‐seq) analysis visualized by Uniform Manifold Approximation and Projection (UMAP), assigned by specific colors at day 5 and 14 post tamoxifen treatment. The number of cells in the individual cluster is depicted in the figure.
  • C
    Distribution of each cluster across indicated time points after tamoxifen treatment.
  • D
    Bar graph showing the percentage of secretory, DATPs, and AT1 cell clusters in control and Lats1/2 dKO lungs at day 5 and 14 post tamoxifen treatment.
  • E
    Blob plot depicting selected marker genes in cell clusters. Dot size encodes the percentage of cells expressing the gene, and color encodes the average per cell gene expression level.
  • F
    Pseudotime ordering of Scgb1a1 lineage‐labeled cells colored by cluster assignment (right) according to diffusion pseudotime (DPT, left) order.
  • G, H
    Representative IF images of control and Lats1/2 dKO airways at indicated time points post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CLDN4 (for DATPs, white), CC10 (G, green), AGER (H, for AT1 cell, green), and DAPI (blue). Scale bar, 100 μm.
  • I
    Quantification of Scgb1a1 lineage‐labeled tdTomato+CLDN4+ DATPs in (G and H). Data are presented as mean ± SEM (n = 5 mice for each genotype). ***P < 0.001 (Student’s t‐test).