Morphogenesis and regeneration share a conserved core transition cell state program that controls lung epithelial...

Area of Science:

• Developmental biology
• Regenerative medicine
• Lung epithelial biology

Background:

• Transitional cell states are critical for development and regeneration but are poorly understood.
• Lung epithelia arise from distal progenitors undergoing cell fate transitions.
• The specific progenitor cell states and their impact in lung development are largely unknown.

Purpose of the Study:

• To identify and characterize transitional cell states in lung development and regeneration.
• To investigate the role of these transitional states in lung morphogenesis and repair.
• To determine if these progenitor cell states are conserved across species.

Main Methods:

• Identification of a specific progenitor population (Icam1/Nkx2-1).
• Lineage-tracing experiments to track cell fate.
• Functional analyses to assess the role of the transitional program.

Main Results:

• A conserved transitional cell state program was identified in Icam1/Nkx2-1 epithelial progenitors.
• This program is present in both mouse and human lung development and regeneration.
• These progenitors give rise to both airway and alveolar cells, and the transitional program is essential for airway cell specification.

Conclusions:

• A common progenitor cell state with a transitional program regulates lung development and regeneration.
• This unified program is reiterated in distinct processes, suggesting conserved mechanisms.
• Understanding this transitional state offers insights into lung morphogenesis and repair strategies.