2. Academic Validation
  3. Morphogenesis and regeneration share a conserved core transition cell state program that controls lung epithelial cell fate

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

  • Dev Cell. 2025 Mar 24;60(6):819-836.e7. doi: 10.1016/j.devcel.2024.11.017.
Xiangyi Ke 1,  Benjamin van Soldt 2,  Lukas Vlahos 3,  Yizhuo Zhou 4,  Jun Qian 5,  Joel George 6,  Claudia Capdevila 7,  Ian Glass 8,  Kelley Yan 7,  Andrea Califano 9,  Wellington V Cardoso 10
Affiliations

Affiliations

  • 1 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Pharmacology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 2 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 3 Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 4 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Pulmonary & Allergy Critical Care, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 5 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 6 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Digestive and Liver Disease, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 7 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Digestive and Liver Disease, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 8 Birth Defects Research Laboratory (BDRL), University of Washington, Seattle, WA 98105, USA.
  • 9 Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • 10 Columbia Center for Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Pulmonary & Allergy Critical Care, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: wvc2104@cumc.columbia.edu.
PMID: 39667932 DOI: 10.1016/j.devcel.2024.11.017
Abstract

Transitional cell states are at the crossroads of crucial developmental and regenerative events, yet little is known about how these states emerge and influence outcomes. The alveolar and airway epithelia arise from distal lung multipotent progenitors, which undergo cell fate transitions to form these distinct compartments. The identification and impact of cell states in the developing lung are poorly understood. Here, we identified a population of Icam1/Nkx2-1 epithelial progenitors harboring a transitional state program remarkably conserved in humans and mice during lung morphogenesis and regeneration. Lineage-tracing and functional analyses reveal their role as progenitors to both airways and alveolar cells and the requirement of this transitional program to make distal lung progenitors competent to undergo airway cell fate specification. The identification of a common progenitor cell state in vastly distinct processes suggests a unified program reiteratively regulating outcomes in development and regeneration.

Keywords

epithelial cell fate; human lung development; lung repair-regeneration; morphogenesis; organoids; single-cell analysis; stem cell; transitional cell state.

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