can engraft into damaged tissue and replace lost cells over the long term but until efficient and quantitative assays are available for the lung, this criterion will be hard to apply. From another point of view, there is growing evidence that cells in “transitional states” between different cell types, including stem cells, may, under certain conditions, accumulate and potentially promote pathological changes in damaged tissue [38, 39]. The chapters in this Monograph contain many examples of how technical and conceptual breakthroughs over the past decade have advanced our understanding of lung stem cells and the mechanisms that control their proliferation and differentiation. It is almost certain that similar innovations over the next 10 years will have an enormous impact on our use of lung stem cells for therapeutic purposes. Some of the ways in which this may happen are discussed in several chapters as well as the final chapter. References 1. Cable J, Fuchs E, Weissman I, et al. Adult stem cells and regenerative medicine a symposium report. Ann N Y Acad Sci 2020 1462: 27–36. 2. Herriges M, Morrisey EE. Lung development: orchestrating the generation and regeneration of a complex organ. Development 2014 141: 502–513. 3. Morrisey EE, Hogan BLM. Preparing for the first breath: genetic and cellular mechanisms in lung development. Dev Cell 2010 18: 8–23. 4. Chacón-Martínez CA, Koester J, Wickström SA. Signaling in the stem cell niche: regulating cell fate, function and plasticity. Development 2018 145: dev165399. 5. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978 4: 7–25. 6. Barkauskas CE, Chung M-I, Fioret B, et al. Lung organoids: current uses and future promise. Development 2017 144: 986–997. 7. Kim J, Koo B-K, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol 2020 21: 571–584. 8. Sellgren KL, Butala EJ, Gilmour BP, et al. A biomimetic multicellular model of the airways using primary human cells. Lab Chip 2014 14: 3349–3358. 9. Clevers H, Watt FM. Defining adult stem cells by function, not by phenotype. Annu Rev Biochem 2018 87: 1015–1027. 10. Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol 2015 16: 27–35. 11. Simons BD, Clevers H. Strategies for homeostatic stem cell self-renewal in adult tissues. Cell 2011 145: 851–862. 12. McKinley KL, Castillo-Azofeifa D, Klein OD. Tools and concepts for interrogating and defining cellular identity. Cell Stem Cell 2020 26: 632–656. 13. Mesa KR, Kawaguchi K, Cockburn K, et al. Homeostatic epidermal stem cell self-renewal is driven by local differentiation. Cell Stem Cell 2018 23: 677–686. 14. Rompolas P, Mesa KR, Kawaguchi K, et al. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis. Science 2016 352: 1471–1474. 15. Ge Y, Fuchs E. Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer. Nat Rev Genet 2018 19: 311–325. 16. Tata PR, Rajagopal J. Cellular plasticity: 1712 to the present day. Curr Opin Cell Biol 2016 43: 46–54. 17. Tata A. Stem cells of submucosal glands: their function as tissue stem cells and a reserve population for airway repair. In: Nikolić MZ, Hogan BLM, eds. Lung Stem Cells in Development, Health and Disease (ERS Monograph). Sheffield, European Respiratory Society, 2021 pp. 70–83. 18. Pai AC, Parekh KR, Engelhardt JF, et al. Ferret respiratory disease models for the study of lung stem cells. In: Nikolić MZ, Hogan BLM, eds. Lung Stem Cells in Development, Health and Disease (ERS Monograph). Sheffield, European Respiratory Society, 2021 pp. 273–289. 19. Lin B, Sun J, Mou H, et al. Adult mouse and human airway epithelial basal stem cells. In: Nikolić MZ, Hogan BLM, eds. Lung Stem Cells in Development, Health and Disease (ERS Monograph). Sheffield, European Respiratory Society, 2021 pp. 56–69. 20. Meyer KB, Wilbrey-Clark A, Nawijn M, et al. The Human Lung Cell Atlas: a transformatioinal resource for cells of the respiratory system. In: Nikolić MZ, Hogan BLM, eds. Lung Stem Cells in Development, Health and Disease (ERS Monograph). Sheffield, European Respiratory Society, 2021 pp. 158–174. xii https://doi.org/10.1183/2312508X.10002321
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