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Airway secretory cell-derived p63+ progenitors contribute to alveolar regeneration after sterile lung injury

Lv, Z.; Liu, Z.; Liu, K.; Pu, W.; Li, Y.; Zhao, H.; Xi, Y.; Vaughan, A.; Gillich, A.; Zhou, B.

2023-02-27 cell biology
10.1101/2023.02.27.530122 bioRxiv
Show abstract

Lung injury activates epithelial stem or progenitor cells for alveolar repair and regeneration. However, the origin and fate of injury-induced progenitors are poorly defined. Here, we report that p63-expressing progenitors emerge upon bleomycin-induced lung injury. These p63+ progenitors proliferate rapidly and differentiate into alveolar type 1 (AT1) and type 2 (AT2) cells through distinct trajectories. Dual recombinase-mediated sequential genetic lineage tracing reveals that p63+ progenitors originate from airway secretory cells and subsequently generate alveolar cells. Functionally, p63 activation is required for efficient alveolar regeneration from secretory cells. Our study identifies a secretory cell-derived p63+ progenitor that contributes to alveolar repair, indicating a potential therapeutic avenue for lung regeneration after injury.

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