Fig. 7: Genetic deletion of Nkx2-1 in vivo leads to loss of distal lung fate and acquisition of PATS/Krt8+ state. | Nature Communications

Fig. 7: Genetic deletion of Nkx2-1 in vivo leads to loss of distal lung fate and acquisition of PATS/Krt8+ state.

From: Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration

Fig. 7

A, B Experimental design of in vivo genetic ablation of Nkx2-1 in AEPs. Mouse genetic construct (A) and experimental treatment plan and schematic (B). 8–12-week Tfcp2l1-CreERT2; R26REYFP (C–F) and Tfcp2l1-CreERT2; R26REYFP; Nkx2-1fl/fl (G–N) were treated with three doses of IP tamoxifen (50 mg/kg) and harvested at 2 to 4 weeks post-treatment; control is from 2-week time point. C Control (Tfcp2l1-CreERT2; R26REYFP) mice exhibited YFP induction in a subset of AT2 cells (SPC+ [red]/Nkx2-1+ [white]) with normal histological characteristics. G, H, K, L Nkx2-1 KO (Tfcp2l1-CreERT2; R26REYFP; Nkx2-1fl/fl) mice exhibited clustered YFP+ proliferative clones negative for AT2 cell markers (SPC− [red]/Nkx2-1− [white], H, L), with acquisition of Ki67 and Krt8 expression (I, J, M, N). Progressive clonal enlargement by 4 weeks post-treatment (K) disrupts normal lung morphology, with continued growth and proliferation. Data throughout the figure represents 3 biological replicates with 3–5 animals per experiment. [Scale bars = 50 µm]. Schematics created with Biorender.com.

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