Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures - INRA - Institut national de la recherche agronomique Accéder directement au contenu
Article Dans Une Revue Development (Cambridge, England) Année : 2019

Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures

Ignacio Caballero
Charles-Hugo Marquette
Brice Marcet

Résumé

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/TGFβ 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.
Fichier principal
Vignette du fichier
Garcia_Caballero_Development_2019_vol-146_art-dev.177428_1.pdf (14.62 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02628140 , version 1 (26-05-2020)

Licence

Paternité

Identifiants

Citer

Sandra Ruiz Garcia, Marie Deprez, Kevin Lebrigand, Amelie Cavard, Agnès Paquet, et al.. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development (Cambridge, England), 2019, 146 (20), 17p. ⟨10.1242/dev.177428⟩. ⟨hal-02628140⟩
67 Consultations
83 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More