REVIEW article
Front. Cell Dev. Biol.
Sec. Morphogenesis and Patterning
Transcriptional Coordination in Multicellular Lineage Differentiation During Lung Organogenesis: Deciphering the Role of Epithelial Cells as a Microenvironmental Regulatory Hub
Provisionally accepted
- 1Tianjin University, Tianjin, China
- 2Tianjin Fifth Central Hospital, Tianjin, China
- 3North China University of Science and Technology, Tangshan, China
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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.
Keywords: cell types, differentiation trajectory, Epithelial Cells, lung development, Omics analysis, regulatory mechanisms
Received: 02 Nov 2025; Accepted: 12 Jan 2026.
Copyright: © 2026 Zhang, Liu, Li, Han, Liu, Zheng and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaozhi Liu
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