A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development

Julie Lee, Andreas Fønss Møller, Shinhyeok Chae, Alexandra Bussek, Tae Joo Park, Youni Kim, Hyun Shik Lee, Tune H. Pers, Taejoon Kwon, Jakub Sedzinski*, Kedar Nath Natarajan*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The specialized cell types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying multipotent early epithelial progenitors that execute multilineage cues before specializing into late-stage ionocytes and goblet and basal cells. Combining in silico lineage inference, in situ hybridization, and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors and chart cell type emergence and fate progression into specialized cell types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programs across vertebrates. We uncover a continuous nonhierarchical model of MCE development alongside a data resource for understanding respiratory biology.

Original languageEnglish
Article numbereadd5745
JournalScience Advances
Volume9
Issue number14
Number of pages22
ISSN2375-2548
DOIs
Publication statusPublished - 7. Apr 2023

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