Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration

Abstract

The mammalian lung epithelium is composed of a wide array of specialized cells that have adapted to survive environmental exposure and perform the tasks necessary for respiration. Although the majority of these cells are remarkably quiescent during adult lung homeostasis, a growing body of literature has demonstrated the capacity of these epithelial lineages to proliferate in response to injury and regenerate lost or damaged cells. In this review, we focus on the regionally distinct lung epithelial cell types that contribute to repair after injury, and we address current controversies regarding whether elite stem cells or frequent facultative progenitors are the predominant participants. We also shed light on the newly emerging approaches for exogenously generating similar lung epithelial lineages from pluripotent stem cells.

Keywords: epithelium; homeostasis; lung; niche; repair; stem/progenitor cells.

Figure 1

Epithelial cell types of the murine lung and their progenitor capacity. (a) The murine lung contains a diverse population of epithelial lineages that are each restricted to specific compartments of the respiratory system. (b) While the lung is largely quiescent during homeostasis, many of these lineages may serve as facultative progenitors capable of self-renewal and differentiation following injury or transplantation. Abbreviations: AEC, alveolar epithelial cell; BASC, bronchioalveolar stem cell; LNEP, lineage-negative epithelial progenitor.

Figure 2

Directed differentiation of pluripotent stem cells (PSCs) to generate lung epithelial lineages. This schematic provides an overview of the major signaling factors utilized during directed differentiation of human or murine PSCs into lung epithelial lineages. The lung epithelial marker Nkx2-1⁺ is first detected upon lung epithelial specification (green background). Depending on the protocol used and the duration of Wnt (or CHIR) treatment (red arrows), it is possible to generate cells similar to alveolar epithelial type 2 cells (AEC2s), airway epithelial lineages, or a mixture of both populations. Superscript numbers denote references.