Progenitor-progeny relationships in airway epithelium.

Scott H. Randell, Ph.D. M any disease processes in airways are characterized by altered epithehial cell phenotype. The spectrum ranges from loss of cilia through mucous cell hypertrophy, hyperplasia, and squamous metaplasia to neoplasia. A useful step toward understanding the regulation of airway cell proliferation and differentiation is elucidation of progenitorprogeny relationships. The current prospect of gene therapy makes this especially important. Lasting therapeutic effect can only be expected if transgenes are incorporated into progenitor cells with extensive proliferative capacity, and they are appropriately expressed in differentiated progeny. It is not clear which tracheobronchial cell type(s) have to be targeted, for example, to produce lasting gene therapy for cystic fibrosis. In bronchioles, Clara cells divide and differentiate into ciliated cells,’ and in the alveoli, the same relationship exists between type H and type I cells.2 There are 3 major cell types in the tracheobronchial airways: basal, secretory, and ciliated cells. Ciliated cells are considered to be terminally differentiated, although there has been some recent data to the contrary.34 There is ample evidence that both basal and secretory cells can divide but the important question of whether the stem cell resides within the basal or secretory cell pool remains unanswered. The predominant cellular pathways of differentiation during development, steady-state renewal in the adult, and following injury are not completely clear. It is necessary to view progenitor-progeny relationships in airway epithehium in the context of current concepts of