Repairing the lungs one breath at a time: How dedicated or facultative are you?

Abstract

Tissue regeneration involves various types of cellular and molecular responses depending on the type of tissue and the injury or disease that is inflicted. While many tissues contain dedicated stem/progenitor cell lineages, many others contain cells that, during homeostasis, are considered physiologically functional and fully differentiated but, after injury or in disease states, exhibit stem/progenitor-like activity. Recent identification of subsets of defined cell types as facultative stem/progenitor cells has led to a re-examination of how certain tissues respond to injury to mount a regenerative response. In this review, we focus on lung regeneration to explore the importance of facultative regeneration controlled by functional and differentiated cell lineages as well as how they are positioned and regulated by distinct tissue niches. Additionally, we discuss the molecular signals to which cells respond in their differentiated state during homeostasis and those signals that promote effective regeneration of damaged or lost cells and structures after injury.

Bi-directional differentiation of single bronchioalveolar stem cells during lung repair

“…Multiple stem or progenitor cells are required for maintaining lung functions during normal condition and repair. The maintenance and repair of epithelium at different regions mainly depend on its resident stem or progenitor cells [1][2][3] .…”

Cells of origin of lung cancers: lessons from mouse studies

“…In contrast to some other tissues that show very high rates of turnover, such as the hematopoietic system and the intestinal tract, the turnover of lung tissue is relatively slow, with a turnover time of 7 yr in humans. However, upon injury, the tissue has the capacity to quickly repair the damage through the mobilization of resident cells with tissue stem cell properties (Rawlins and Hogan 2006;Kim 2017;Leach and Morrisey 2018;Lee and Rawlins 2018). These specialized cells, such as basal cells and subsets of alveolar type II (AT2) cells, are capable of giving rise to the diverse lineages that line the different anatomical compartments of the respiratory system.…”

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

“…Recent evidence shows that individual AT-II Axin2+ stem cells reside in single-cell fibroblast niches providing juxtacrine Wnt signaling that maintains them as stem cells during homeostasis [43]. Lung injury induces the secretion of autocrine Wnt, allowing proliferation in response to mitogens and expansion of the progenitor pool [43,44]. It has been suggested that the inability of exhausted AT-II to trans-differentiate into AT-I and to regenerate the epithelial layer after continuous damage may cause aberrant activation of the physiological signaling pathways upstream of this process [10,16,45], which eventually leads to fibrosis.…”