# Transcriptional coordination in multicellular lineage differentiation during lung organogenesis: deciphering the role of epithelial cells as a microenvironmental regulatory hub

## TL;DR

This review explores how epithelial cells guide lung development by controlling cell differentiation and signaling during organ formation.

## Contribution

The paper highlights the dual regulatory role of epithelial cells in lung development and their impact on cell fate and regeneration.

## Key findings

- Epithelial cells act as a central hub regulating spatial patterning and cell differentiation during lung development.
- They orchestrate developmental fates through multiple signaling cues and influence stem cell regenerative properties.
- The insights may improve strategies for lung regeneration and disease intervention.

## Abstract

Lung development is a complex and precisely regulated process of continuously branching morphogenesis, the core of which lies in the directed differentiation of diverse cell types and the dynamic intercellular interaction network. This review systematically delineates the differentiation pathways of major cellular lineages during pulmonary development, with a particular focus on the dual functions of epithelial cells as the core regulatory hub of the microenvironment. These cells not only dominate the spatial patterning of lung branching morphogenesis but also orchestrate the developmental fates of key cell types through multiple signaling cues. Furthermore, this review discusses the regenerative properties of lung-resident stem cells and the interaction patterns between various cell types and epithelial cells. These insights not only provide an important theoretical framework for elucidating the molecular regulatory network of lung development but also offer novel ideas for the optimization of strategies in lung regenerative medicine and the precision intervention for lung-related diseases.