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Cell Atlas of Human Lung Development Gives View of Developing Airway

A cell atlas of human lung development built using sequencing, transcriptomic, and single-cell imaging technologies is presented in Cell this week, offering views of the various states of the developing airway. Single-cell mapping of cell states in the adult human lung can help advance understanding of lung cellular physiology, but the low rates of cell turnover in the adult lung has made it difficult to capture transition states and progenitors. Additionally, there are developmental-specific cell states that just do not exist in adults. Aiming to address these issues, a team led by scientists from the University of Cambridge and the Wellcome Sanger Institute used a combination of single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging to create a spatiotemporal atlas of lung development that identifies 144 cell types or states in fetal lung samples from five to 22 weeks post-conception. These include previously uncharacterized progenitor cell states, transition populations, and a subtype of neuroendocrine cell related to a subtype of human small cell lung cancer. Using the resource, the researchers tracked increasing cell maturation over time and make predictions about progenitor cell states, signaling interactions, and lineage-defining transcription factors, which they tested in organoid models.