Fig. 6.4.

Small airway bronchiolar and alveolar lineages. (a) Basal-like progenitors are rare in small airways, yet they play an important role in restoring the structural integrity of alveolar epithelium after catastrophic viral injury (green arrow) by generating KRT5+ alveolar pods [58–60]. Recent evidence also suggests that small airway basal-like cells give rise to bronchiolar club cells [7]. (b) A rare subtype of club cells expressing Uroplakin3a (U-Club cells) is capable of renewing the larger club cell population at steady state. Following naphthalene injury (red arrow), U-club cells can also give rise to multiciliated cells, and following bleomycin injury (yellow arrow), U-Club cells renew alveolar type 2 (AT2) cells [61]. (c) The alveolar epithelium consists of AT2 cells and alveolar type 1 (AT1) cells, and AT2 cells are self-renewing and can lineage commit to AT1 cells [62]. Recently, a population of highly clonogenic stem cells called alveolar epithelial progenitors (AEPs) has been identified within the AT2 cell population [63]. In addition, AT1 cells are able to dedifferentiate following severe injury (dashed red arrow) into AT2 cells [64, 65]. (d) In addition, small airways harbor neuroepithelial bodies, which consist of clusters of self-renewing neuroendocrine cells. Forced induction of notch signaling in the context of injury induces neuroendocrine to club-like cell transdifferentiation [66]. During development (blue arrow), solitary neuroendocrine cells residing in proximal airways migrate to small airway branch points where they organize into neuroepithelial bodies [67]