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Review
. 2017 Mar 1;144(5):755-766.
doi: 10.1242/dev.143784.

Plasticity in the lung: making and breaking cell identity

Purushothama Rao Tata  1   2   3 , Jayaraj Rajagopal  4   2   3   5   6
Affiliations
Review

Plasticity in the lung: making and breaking cell identity

Purushothama Rao Tata et al. Development. .

Abstract

In contrast to a prior emphasis on the finality of cell fate decisions in developmental systems, cellular plasticity is now emerging as a general theme in the biology of multiple adult organ systems. In the lung, lineage tracing has been used to identify distinct epithelial stem and progenitor cell populations. These cells, together with their differentiated progeny, maintain a stable identity during steady state conditions, but can display remarkable lineage plasticity following injury. This Review summarizes our current understanding of the different cell lineages of the adult mammalian lung and their responses to injury. In the lung, which is constantly exposed to infection and aerosolized toxins, epithelial plasticity might be more of a rule than an exception, and it is likely that different injuries elicit different facultative responses.

Keywords: Cellular heterogeneity; Cellular plasticity; Lineage tracing; Lung injury repair; Lung regeneration; Lung stem cells.

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Conflict of interest statement

Competing interests

The authors declare no competing or financial interests.

Figures

Fig. 1.
Fig. 1.
Anatomical and cellular differences between murine and human lung. The respiratory tree consists of two distinct regions: airways and alveoli. Within airways, distinct compartments contain different cell populations that vary along the proximodistal axis. In human airways, basal cells extend throughout the small airways, whereas in mouse, basal cells extend only up to the mainstem bronchi. In humans, cartilage rings span several generations of airway, whereas in mouse, cartilage rings are present only in the trachea and mainstem bronchi. In humans, submucosal glands are present throughout many small airways, whereas in mice submucosal glands are restricted to the proximal domains of the trachea. The distribution of other various cell types is also indicated in the schematics. Notably, whereas much of the small airway in mouse is composed of a cuboidal epithelium consisting mainly of ciliated and secretory cells, in the human such epithelium is restricted to only the very most distal cells of the bronchioalveolar duct junction.
Fig. 2.
Fig. 2.
Lineage hierarchies in lung epithelial tissues. (A-C) Epithelial lineages in the large airways (A), in the small airways (B) and in the alveoli (C). Bold curved arrows indicate high self-renewal potential whereas dotted curved arrows indicate limited self-renewal potential.
Fig. 3.
Fig. 3.
Injury-induced lineage plasticity of differentiated cells. (A) In the airways, following ablation of the basal cell population (green), lineage-labeled secretory cells (purple) undergo de-differentiation into basal cells, thereby repopulating the stem cell compartment. (B) In the alveoli, Hopx+ alveolar type 1 cells replicate and generate alveolar type 2 cells following pneumonectomy.
Fig. 4.
Fig. 4.
Intercellular communication restricts lineage plasticity in the airway. Schematic of the role of cell-cell communication between parent and daughter cells, and its effect on daughter cell plasticity as demonstrated in ex vivo organoid assays. In the top scenario, organoids that originate solely from basal cells contain both basal and secretory cell types. In the middle scenario, organoids that originate from both basal and secretory cells contain both cell types, but the secretory cells do not de-differentiate in the presence of basal cells and basal cells do not differentiate into secretory cells. In the third scenario, organoids that originate solely from secretory cells contain both secretory and basal cell types demonstrating that secretory cells can de-differentiate into basal cells in this environment.
Fig. 5.
Fig. 5.
Cellular responses of LNEPs/DASCs following H1N1 influenza-induced alveolar injury. (A) Schematic of the appearance of basal-like cells in pods following H1N1 infection in murine models. Three different cell populations, namely LNEPs, DASCs and Sox2+Lin− cells, were recently proposed to respond to H1N1 influenza injury and form KRT5+p63+ epithelial pods in areas with alveolar damage. It is very likely that all these populations have a high degree of overlap, and furthermore that each is divisible into further subsets of progenitor cells. (B) Schematic of the fate of the KRT5+p63+ pod cells following H1N1 influenza injury. Pod cells do not regenerate alveoli following H1N1 infection.
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