Regeneration of airway epithelial cells to study rare cell states in cystic fibrosis

Abstract

a b s t r a c tPathological remodeling of the airway epithelium is commonly observed in cystic fibrosis (CF). Thus, tissue repair is critical to restore integrity and maintenance of the epithelial barrier function. Epithelial repair is a multi-step process initiated by progenitor cell migration into the injured area, proliferation, and re-differentiation into all of the cell types that contribute to the function of a normal airway epithelium. Recent technological advances applied to relevant animal and cell injury models have helped in understanding the complexity of progenitor cell differentiation. This short review will introduce the current knowledge of the mechanisms regulating airway epithelial cell (AEC) regeneration and repair, with a focus on the specification of two rare cell types/states: ionocytes and deuterosomal cells.

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

“…Thereafter, epithelial cells start to re-differentiate until they are completely differentiated, thus reconstituting a polarized and intact epithelium. [118][119][120]. CFTR was first implicated in tissue regeneration by studies in rat livers.…”

Vav3 Mediates Pseudomonas aeruginosa Adhesion to the Cystic Fibrosis Airway Epithelium

“…This repair process was associated with de-differentiation and loss of polarity of airway epithelial cells (Hé rard et al, 1996). Since CFTR may contribute to airway epithelial repair and regeneration (Barbry et al, 2019), it is tempting to speculate that Vav3 deregulation in CF is a consequence of abnormal airway epithelial cell differentiation.…”

Exploring the basic mechanisms in Cystic Fibrosis: Promoting data presentation and discussion at the 16th ECFS Basic Science Conference

“…Lung pathology progression and disease severity in CF is linked to pathological remodeling of the airway epithelium. The article by Barbry and colleagues [26] gives an overview of the current knowledge on the mechanisms regulating airway epithelial cell regeneration and repair, which is a multi-step process leading to the redifferentiation of progenitor cells into all cell types contributing to the function of the normal epithelia. The article especially focuses on pulmonary ionocytes and deuterosomal cells, two recently described airway cell types identified by powerful single-cell RNA-sequencing techniques and suggested to have great relevance for CF [27][28][29].…”

“…The article by Boyd and colleagues [36] more specifically focuses on the potential of ENaC siRNA targeting and antisense oligonucleotide approaches to CF therapy, as well as those offered by plasmid-mediated therapies using viral or non-viral liposomal vectors, with initial data highlighting a favorable effect of gene therapy on the modulation of lung function. Questions remain relative to the challenges of delivery and to the cell-types which have to be targeted in the epithelium for such genetic therapies, given that the airway epithelium contains high and low-CFTR expressing cells, each playing distinct roles in the physiology and protection from infection [26,37].…”