ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury | JoVE Visualize

ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury

Aaron I Weiner¹, Gan Zhao¹, Hanna M Zayas²

¹Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cell Reports|December 14, 2022

View abstract on PubMed

Summary

The transcription factor ΔNp63 in basal lung progenitors drives abnormal tissue repair after injury. Removing ΔNp63 allows these cells to regenerate functional lung alveoli, offering therapeutic potential.

Area of Science:

Pulmonary Medicine
Cell Biology
Regenerative Medicine

Background:

Severe lung injuries, like influenza, trigger complex regenerative responses.
Lung repair involves both beneficial alveolar regeneration and detrimental dysplastic remodeling.
Airway-resident basal progenitors play a role in aberrant tissue repair.

Purpose of the Study:

To investigate the role of the basal cell transcription factor ΔNp63 in lung repair.
To understand how ΔNp63 influences the fate of intrapulmonary basal progenitors.
To identify mechanisms governing dysplastic versus functional lung regeneration.

Main Methods:

Utilized mouse models of lung injury.
Examined the function of ΔNp63 in intrapulmonary basal progenitors.
Analyzed histone modifications at differentiation gene loci.
Performed in vitro and in vivo experiments to assess progenitor cell plasticity.

Main Results:

ΔNp63 is essential for basal progenitors to drive dysplastic alveolar remodeling.
ΔNp63 maintains progenitor cell fate by regulating histone modifications.
Loss of ΔNp63 enables basal progenitors to differentiate into either airway or alveolar cells based on environmental cues.
Demonstrated progenitor plasticity following ΔNp63 deletion both in vitro and in vivo.

Conclusions:

ΔNp63 acts as a key regulator restricting basal progenitor plasticity and promoting dysplastic lung repair.
Targeting ΔNp63 may offer a strategy to promote functional alveolar regeneration after lung injury.
Understanding basal cell fate determination is crucial for developing therapies for lung diseases.