Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity

Henry Quach, Spencer Farrell, Ming Jia Michael Wu, Kayshani Kanagarajah, Joseph Wai-Hin Leung, Xiaoqiao Xu, Prajkta Kallurkar, Andrei L. Turinsky, Christine E. Bear, Felix Ratjen, Brian Kalish, Sidhartha Goyal, Theo J. Moraes and Amy P. Wong ()
Additional contact information
Henry Quach: Hospital for Sick Children
Spencer Farrell: University of Toronto
Ming Jia Michael Wu: Hospital for Sick Children
Kayshani Kanagarajah: Hospital for Sick Children
Joseph Wai-Hin Leung: Hospital for Sick Children
Xiaoqiao Xu: Hospital for Sick Children
Prajkta Kallurkar: Hospital for Sick Children
Andrei L. Turinsky: Hospital for Sick Children
Christine E. Bear: Hospital for Sick Children
Felix Ratjen: Hospital for Sick Children
Brian Kalish: Hospital for Sick Children
Sidhartha Goyal: University of Toronto
Theo J. Moraes: Hospital for Sick Children
Amy P. Wong: Hospital for Sick Children

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: Abstract Studying human fetal lungs can inform how developmental defects and disease states alter the function of the lungs. Here, we sequenced >150,000 single cells from 19 healthy human pseudoglandular fetal lung tissues ranging between gestational weeks 10–19. We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR). These cells give rise to multiple specialized epithelial cell types. Combined with spatial transcriptomics, we show temporal regulation of key signalling pathways that may drive the temporal and spatial emergence of specialized epithelial cells including ciliated and pulmonary neuroendocrine cells. Finally, we show that human pluripotent stem cell-derived fetal lung models contain CFTR-expressing progenitor cells that capture similar lineage developmental trajectories as identified in the native tissue. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from human pluripotent stem cell differentiations to similar developmental window.

Date: 2024
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DOI: 10.1038/s41467-024-50281-5

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