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. Author manuscript; available in PMC: 2022 Oct 26.
Published in final edited form as: Cells Tissues Organs. 2021 Apr 26;211(6):736–753. doi: 10.1159/000514579

Figure 5: Mucociliary cell lineages and signaling in development, homeostasis and remodeling.

Figure 5:

(A-E) Simplified schematic representation of mucociliary cell types (cf. Figure 1 E for legend) and their specification or trans-differentiation during normal development and homeostasis as well as in experimental models of inflammation, remodeling and severe injury. (A) In mammalian airway development, basal cells can self-renew and generate all epithelial cell types. (B) In mammalian airway homeostasis and repair, basal cells, club cells, PNECs and goblet cells can self-renew. Additionally, MCCs and goblet cell populations can be maintained by trans-differentiation from club cells. In the submucosal glands, mucous cells are generated from myoepithelial cells. (C) Trans-differentiation events in mammalian airway inflammation, tissue remodeling (e.g. in chronic airway disease), and after experimental manipulation. Club cells can trans-differentiate into MCCs, goblet cells, and can de-differentiate into basal cells upon severe basal cell loss. After severe injury, PNECs can also trans-differentiate into club cells. Trans-differentiation between MCC and goblet cell fates were reported in both directions. Myoepithelial cells in the submucosal glands can generate mucous cells, but also trans-differentiate into epithelial basal cells after severe basal cell loss. (D) Mucociliary development in the Xenopus embryonic mucociliary epidermis. All epithelial cell types are derived from precursor cells that mature into basal cells. Basal cells and goblet cells can both divide and self-renew. (E) Multiciliated to goblet cell trans-differentiation at the onset of Xenopus metamorphosis was demonstrated in the Xenopus epidermis, is triggered by increased Notch signaling and modulated by thyroid hormone and Jak/Stat signlaing. Black arrows = cell type transitions from stem/precursor cells; blue arrows = proliferation/self-renewal; red arrows = trans- and de-differentiation events. * = in the bronchiole only; ** = in the submucosal glands only.