Plasticity in airway smooth muscle differentiation during mouse lung development

Area of Science:

• Developmental Biology
• Cell Biology
• Pulmonary Medicine

Background:

• Airway branching morphogenesis is crucial for mammalian lung development.
• Smooth muscle differentiation is proposed to physically sculpt airway branches.
• Serum response factor (SRF) and myocardin typically regulate contractile smooth muscle markers.

Purpose of the Study:

• To investigate the role of SRF in embryonic airway smooth muscle development and its impact on lung branching.
• To determine if embryonic airway smooth muscle exhibits phenotypic plasticity similar to adult smooth muscle.

Main Methods:

• Deletion of Srf gene from mouse embryonic pulmonary mesenchyme.
• Analysis of lung branching and mesenchyme mechanical properties in Srf-mutant embryos.
• Single-cell RNA sequencing (scRNA-seq) to characterize smooth muscle cell phenotypes.

Main Results:

• Srf-mutant lungs exhibited normal branching and mesenchyme mechanics.
• scRNA-seq revealed an Srf-null smooth muscle cell cluster lacking contractile markers but retaining other smooth muscle features.
• Embryonic airway smooth muscle in Srf-mutants displayed a synthetic phenotype, contrasting with the contractile phenotype of wild-type mature smooth muscle.

Conclusions:

• Embryonic airway smooth muscle demonstrates significant phenotypic plasticity.
• A synthetic smooth muscle layer, independent of SRF-mediated transcription, can promote airway branching morphogenesis.
• This suggests a novel mechanism for airway development involving adaptable smooth muscle phenotypes.