Hippo signaling impairs alveolar epithelial regeneration in pulmonary fibrosis

  1. Rachel Warren
  2. Handeng Lyu
  3. Kylie Klinkhammer
  4. Stijn P De Langhe  Is a corresponding author
  1. Department of Medicine, Division of Pulmonary and Critical Medicine, Mayo Clinic, United States
7 figures and 1 additional file

Figures

Hippo pathway expression in the lung.

Single nuclei RNA-seq was performed on E18.5 lungs. (Top and middle row) Cell types were identified based on gene expression: Sftpc (AT2); Lmo7, Rtkn2 (AT1); Pecam1 (endothelial); Lgr6 …

The Hippo pathway is active in alveolar type 2 (AT2) cells but not in AT1 cells.

Left lung lobes of 8-week-old mice were inflation fixed, embedded in paraffin, and sectioned. (A–C) Immunostaining for Sftpc (A–C), Merlin (A, C), and Scgb1a1 (B, C) and (D–F) immunostaining for …

The Hippo pathway actively maintains alveolar type 2 (AT2) cells during homeostasis.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and left lung lobes were inflation fixed, embedded in paraffin, and sectioned 9 weeks after being placed on normal chow (at 20 …

Figure 4 with 2 supplements
Taz is required for alveolar type 2 (AT2) into AT1 cell differentiation following bleomycin injury.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were injured with intratracheal administration of bleomycin. At 6 weeks post-injury (at …

Figure 4—figure supplement 1
Inactivation of Stk3/4 promotes fibrosis resolution 6 weeks after bleomycin injury.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 3 or 6 …

Figure 4—figure supplement 2
Inactivation of Yap1 in alveolar type 2 (AT2) induces Taz upregulation.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were injured with intratracheal administration of bleomycin. At 6 weeks post-injury (at …

Figure 5 with 1 supplement
Decreased alveolar epithelial regeneration following bleomycin injury upon inactivation of Yap/Taz in alveolar type 2 (AT2) cells.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 6 weeks …

Figure 5—figure supplement 1
Alveolar type 2 (AT2) inactivation of Yap1/Wwtr1 reduces the S phase after bleomycin injury.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 6 weeks …

Figure 6 with 1 supplement
Increased bronchiolization upon Yap/Taz inactivation in alveolar type 2 (AT2) cells.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 6 weeks …

Figure 6—figure supplement 1
Repetitive bleomycin doses induce bronchiolization.

Mice were administered bleomycin intratracheally beginning at 8 weeks of age. Every 2 weeks mice received additional doses of bleomycin for either 3 or 5 doses. Left lung lobes were inflation fixed, …

Figure 7 with 2 supplements
Inactivation of Yap and Taz in alveolar type 2 (AT2) cells enhances bronchiolization following bleomycin injury.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were injured with intratracheal administration of bleomycin. At 6 weeks post-injury (at …

Figure 7—figure supplement 1
Predicted transcription factor expression.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 6 weeks …

Figure 7—figure supplement 2
Predicted transcription factor expression is altered based on genotype and injury status.

At 8 weeks of age, mice were placed on tamoxifen chow for 3 weeks, and following a 3-week washout period, mice were non-injured or injured with intratracheal administration of bleomycin. At 6 weeks …

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