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Related Experiment Video

Updated: Oct 1, 2025

Mouse Embryonic Lung Culture, A System to Evaluate the Molecular Mechanisms of Branching
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Patterning the embryonic pulmonary mesenchyme.

Katharine Goodwin1, Jacob M Jaslove2,3, Hirotaka Tao4

  • 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

Iscience
|March 7, 2022
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Summary

Airway smooth muscle development is guided by mesenchymal cells, not distinct progenitors. Wnt signaling patterns these cells, influencing airway epithelial shape and smooth muscle differentiation.

Keywords:
Cell biologyDevelopmental biologyTranscriptomics

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Area of Science:

  • Developmental biology
  • Cell biology
  • Organogenesis

Background:

  • Smooth muscle is crucial for mammalian airway morphogenesis.
  • The origins and patterning of airway smooth muscle differentiation remain unclear.
  • Distinct mesenchymal progenitors for airway smooth muscle have not been identified.

Purpose of the Study:

  • To investigate the cellular origins and patterning mechanisms of airway smooth muscle differentiation.
  • To identify distinct mesenchymal progenitors in the embryonic lung.
  • To understand the role of Wnt signaling in mesenchymal patterning and smooth muscle development.

Main Methods:

  • Single-cell RNA-sequencing of embryonic mouse lungs.
  • Live-imaging and tension sensors.
  • Computational reconstruction of differentiation trajectories.

Main Results:

  • Pulmonary mesenchyme exhibits a cell identity continuum, not distinct progenitors.
  • Transcriptional variability correlates with spatially distinct mesenchymal compartments regulated by Wnt signaling.
  • Sub-epithelial mesenchyme contributes to airway smooth muscle, exhibiting specific migratory behaviors and forces.
  • Wnt activation promotes early smooth muscle differentiation and mesenchymal F-actin accumulation, influencing epithelial morphology.

Conclusions:

  • Pulmonary mesenchymal patterning is governed by Wnt signaling, creating distinct compartments.
  • A morphogenetically active mesenchymal layer, originating from the sub-epithelial compartment, sculpts the airway epithelium.
  • Smooth muscle differentiation is initiated by Wnt signaling within a continuous mesenchymal population.