Journal
DEVELOPMENT
Volume 146, Issue 20, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.177428
Keywords
Airway epithelium; Single-cell RNA-seq; Differentiation; Multiciliated cells; Club cells; Goblet cells; Basal cells; Deuterosome; Keratins; Pathways
Categories
Funding
- Fondation pour la Recherche Medicale [DEQ20180339158]
- Labex Signalife [ANR-11-LABX-0028-01]
- Association Vaincre la Mucoviscidose [RF20180502280]
- Chan Zuckerberg Initiative (Silicon Valley Community Foundation) [2017-175159-5022]
- Commissariat aux Grands Investissements [ANR-10-INBS-09-03, ANR-10-INBS-09-02]
- Canceropole PACA
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The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGF beta pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation.
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