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  • Review Article
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Lung regeneration: mechanisms, applications and emerging stem cell populations

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Abstract

Recent studies have shown that the respiratory system has an extensive ability to respond to injury and regenerate lost or damaged cells. The unperturbed adult lung is remarkably quiescent, but after insult or injury progenitor populations can be activated or remaining cells can re-enter the cell cycle. Techniques including cell-lineage tracing and transcriptome analysis have provided novel and exciting insights into how the lungs and trachea regenerate in response to injury and have allowed the identification of pathways important in lung development and regeneration. These studies are now informing approaches for modulating the pathways that may promote endogenous regeneration as well as the generation of exogenous lung cell lineages from pluripotent stem cells. The emerging advances, highlighted in this Review, are providing new techniques and assays for basic mechanistic studies as well as generating new model systems for human disease and strategies for cell replacement.

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Figure 1: Relationship between the regenerative capacity of different tissues and the existence of resident tissue-specific stem cells.
Figure 2: Cell lineages in early lung development in mouse.
Figure 3: Stem cell and differentiated epithelial lineages in the trachea and main stem bronchi of the lung.
Figure 4: Stem cell and differentiated epithelial lineages in the bronchiolar airways of the lung.
Figure 5: Progenitor cell populations and their differentiated progeny in the lung alveolus.

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Acknowledgements

The authors would like to thank the members of their laboratories for input and discussion that helped to provide context and edits to this review. E.E.M.'s laboratory is supported by funding from the US National Institutes of Health (NIH) (HL100405, HL110942, HL087825 and HL071589). D.N.K.'s laboratory is supported by funding from the NIH (HL095993, HL122442 and HL108678).

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Correspondence to Darrell N Kotton or Edward E Morrisey.

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Kotton, D., Morrisey, E. Lung regeneration: mechanisms, applications and emerging stem cell populations. Nat Med 20, 822–832 (2014). https://doi.org/10.1038/nm.3642

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