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Annual Review of Physiology

Volume 83, 2021

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.

Keyword(s): epithelium, homeostasis, lung, niche, repair, stem/progenitor cells
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/content/journals/10.1146/annurev-physiol-041520-092904
2021-02-10
2024-04-23
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Literature Cited

  1. 1. 
    Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP et al. 2009. Basal cells as stem cells of the mouse trachea and human airway epithelium. PNAS 106:3112771–75
     [Google Scholar]
  2. 2. 
    Morrison SJ, Uchida N, Weissman IL 1995. The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11:35–71
     [Google Scholar]
  3. 3. 
    Hogan BLM, Barkauskas CE, Chapman HA, Epstein JA, Jain R et al. 2014. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 15:2123–38
     [Google Scholar]
  4. 4. 
    Chiu C, Openshaw PJ. 2014. Antiviral B cell and T cell immunity in the lungs. Nat. Immunol. 16:118–26
     [Google Scholar]
  5. 5. 
    Whitsett JA, Alenghat T. 2014. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat. Immunol. 16:127–35
     [Google Scholar]
  6. 6. 
    Kotton DN, Morrisey EE. 2014. Lung regeneration: mechanisms, applications and emerging stem cell populations. Nat. Med. 20:8822–32
     [Google Scholar]
  7. 7. 
    Zepp JA, Morrisey EE. 2019. Cellular crosstalk in the development and regeneration of the respiratory system. Nat. Rev. Mol. Cell Biol. 20:9551–66
     [Google Scholar]
  8. 8. 
    Basil MC, Katzen J, Engler AE, Guo M, Herriges MJ et al. 2020. The cellular and physiological basis for lung repair and regeneration: past, present, and future. Cell Stem Cell 26:4482–502
     [Google Scholar]
  9. 9. 
    Hogan BLM, Tata PR. 2019. Cellular organization and biology of the respiratory system. Nat. Cell Biol. https://doi.org/10.1038/s41556-019-0357-7
    [Crossref] [Google Scholar]
  10. 10. 
    Pardo-Saganta A, Law BM, Gonzalez-Celeiro M, Vinarsky V, Rajagopal J 2013. Ciliated cells of pseudostratified airway epithelium do not become mucous cells after ovalbumin challenge. Am. J. Respir. Cell Mol. Biol. 48:3364–73
     [Google Scholar]
  11. 11. 
    Reader JR, Tepper JS, Schelegle ES, Aldrich MC, Putney LF et al. 2003. Pathogenesis of mucous cell metaplasia in a murine asthma model. Am. J. Pathol. 162:62069–78
     [Google Scholar]
  12. 12. 
    Evans CM, Williams OW, Tuvim MJ, Nigam R, Mixides GP et al. 2004. Mucin is produced by Clara cells in the proximal airways of antigen-challenged mice. Am. J. Respir. Cell Mol. Biol. 31:4382–94
     [Google Scholar]
  13. 13. 
    Tyner JW, Kim EY, Ide K, Pelletier MR, Roswit WT et al. 2006. Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. J. Clin. Investig. 116:2309–21
     [Google Scholar]
  14. 14. 
    Liu JY, Nettesheim P, Randell SH 1994. Growth and differentiation of tracheal epithelial progenitor cells. Am. J. Physiol. 266:3 Part 1L296–307
     [Google Scholar]
  15. 15. 
    Avril-Delplanque A, Casal I, Castillon N, Hinnrasky J, Puchelle E, Péault B 2005. Aquaporin-3 expression in human fetal airway epithelial progenitor cells. Stem Cells 23:7992–1001
     [Google Scholar]
  16. 16. 
    Johnson NF, Hubbs AF. 1990. Epithelial progenitor cells in the rat trachea. Am. J. Respir. Cell Mol. Biol. 3:6579–85
     [Google Scholar]
  17. 17. 
    Ford JR, Terzaghi-Howe M. 1992. Basal cells are the progenitors of primary tracheal epithelial cell cultures. Exp. Cell Res. 198:169–77
     [Google Scholar]
  18. 18. 
    Evans MJ, Van Winkle LS, Fanucchi MV, Plopper CG 2001. Cellular and molecular characteristics of basal cells in airway epithelium. Exp. Lung Res. 27:5401–15
     [Google Scholar]
  19. 19. 
    Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR 2004. In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations. Am. J. Physiol. Lung Cell. Mol. Physiol. 286:4L643–49
     [Google Scholar]
  20. 20. 
    Teixeira VH, Nadarajan P, Graham TA, Pipinikas CP, Brown JM et al. 2013. Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors. eLife 2:e00966
     [Google Scholar]
  21. 21. 
    Watson JK, Rulands S, Wilkinson AC, Wuidart A, Ousset M et al. 2015. Clonal dynamics reveal two distinct populations of basal cells in slow-turnover airway epithelium. Cell Rep 12:190–101
     [Google Scholar]
  22. 22. 
    Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B et al. 2018. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560:7718319–324
     [Google Scholar]
  23. 23. 
    Plasschaert LW, Žilionis R, Choo-Wing R, Savova V, Knehr J et al. 2018. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature 560:7718377–81
     [Google Scholar]
  24. 24. 
    Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH et al. 2016. Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell 19:2217–31
     [Google Scholar]
  25. 25. 
    Cole BB, Smith RW, Jenkins KM, Graham BB, Reynolds PR, Reynolds SD 2010. Tracheal basal cells: a facultative progenitor cell pool. Am. J. Pathol. 177:1362–76
     [Google Scholar]
  26. 26. 
    Ghosh M, Helm KM, Smith RW, Giordanengo MS, Li B et al. 2011. A single cell functions as a tissue-specific stem cell and the in vitro niche-forming cell. Am. J. Respir. Cell Mol. Biol. 45:3459–69
     [Google Scholar]
  27. 27. 
    Pardo-Saganta A, Law BM, Tata PR, Villoria J, Saez B et al. 2015. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations. Cell Stem Cell 16:2184–97
     [Google Scholar]
  28. 28. 
    Miller AJ, Yu Q, Czerwinski M, Tsai Y-H, Conway RF et al. 2020. In vitro and in vivo development of the human airway at single-cell resolution. Dev. Cell 53:1117–28
     [Google Scholar]
  29. 29. 
    Tadokoro T, Gao X, Hong CC, Hotten D, Hogan BLM 2016. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Development 143:5764–73
     [Google Scholar]
  30. 30. 
    Rock JR, Gao X, Xue Y, Randell SH, Kong Y-Y, Hogan BLM 2011. Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 8:6639–48
     [Google Scholar]
  31. 31. 
    Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL et al. 2009. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4:6525–34
     [Google Scholar]
  32. 32. 
    Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M et al. 2013. Dedifferentiation of committed epithelial cells into stem cells in vivo. . Nature 503:7475218–23
     [Google Scholar]
  33. 33. 
    Borthwick DW, Shahbazian M, Krantz QT, Dorin JR, Randell SH 2001. Evidence for stem-cell niches in the tracheal epithelium. Am. J. Respir. Cell Mol. Biol. 24:6662–70
     [Google Scholar]
  34. 34. 
    Meyrick B, Sturgess JM, Reid L 1969. A reconstruction of the duct system and secretory tubules of the human bronchial submucosal gland. Thorax 24:6729–36
     [Google Scholar]
  35. 35. 
    Borthwick DW, West JD, Keighren MA, Flockhart JH, Innes BA, Dorin JR 1999. Murine submucosal glands are clonally derived and show a cystic fibrosis gene-dependent distribution pattern. Am. J. Respir. Cell Mol. Biol. 20:61181–89
     [Google Scholar]
  36. 36. 
    Innes BA, Dorin JR. 2001. Submucosal gland distribution in the mouse has a genetic determination localized on chromosome 9. Mamm. Genome 12:2124–28
     [Google Scholar]
  37. 37. 
    Hegab AE, Ha VL, Gilbert JL, Zhang KX, Malkoski SP et al. 2011. Novel stem/progenitor cell population from murine tracheal submucosal gland ducts with multipotent regenerative potential. Stem Cells 29:81283–93
     [Google Scholar]
  38. 38. 
    Tata A, Kobayashi Y, Chow RD, Tran J, Desai A et al. 2018. Myoepithelial cells of submucosal glands can function as reserve stem cells to regenerate airways after injury. Cell Stem Cell 22:5668–83
     [Google Scholar]
  39. 39. 
    Lynch TJ, Anderson PJ, Rotti PG, Tyler SR, Crooke AK et al. 2018. Submucosal gland myoepithelial cells are reserve stem cells that can regenerate mouse tracheal epithelium. Cell Stem Cell 22:5653–55
     [Google Scholar]
  40. 40. 
    Reynolds SD, Reynolds PR, Pryhuber GS, Finder JD, Stripp BR 2002. Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways. Am. J. Respir. Crit. Care Med. 166:111498–509
     [Google Scholar]
  41. 41. 
    Guha A, Vasconcelos M, Cai Y, Yoneda M, Hinds A et al. 2012. Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways. PNAS 109:3112592–97
     [Google Scholar]
  42. 42. 
    McCauley KB, Alysandratos K-D, Jacob A, Hawkins F, Caballero IS et al. 2018. Single-cell transcriptomic profiling of pluripotent stem cell-derived SCGB3A2+ airway epithelium. Stem Cell Rep 10:51579–95
     [Google Scholar]
  43. 43. 
    Chen H, Matsumoto K, Brockway BL, Rackley CR, Liang J et al. 2012. Airway epithelial progenitors are region specific and show differential responses to bleomycin-induced lung injury. Stem Cells 30:91948–60
     [Google Scholar]
  44. 44. 
    Guha A, Vasconcelos M, Zhao R, Gower AC, Rajagopal J, Cardoso WV 2014. Analysis of Notch signaling-dependent gene expression in developing airways reveals diversity of Clara cells. PLOS ONE 9:2e88848
     [Google Scholar]
  45. 45. 
    Rawlins EL, Hogan BLM. 2008. Ciliated epithelial cell lifespan in the mouse trachea and lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 295:1L231–34
     [Google Scholar]
  46. 46. 
    Reynolds SD, Giangreco A, Power JH, Stripp BR 2000. Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am. J. Pathol. 156:1269–78
     [Google Scholar]
  47. 47. 
    Guha A, Deshpande A, Jain A, Sebastiani P, Cardoso WV 2017. Uroplakin 3a+ cells are a distinctive population of epithelial progenitors that contribute to airway maintenance and post-injury repair. Cell Rep 19:2246–54
     [Google Scholar]
  48. 48. 
    Hong KU, Reynolds SD, Giangreco A, Hurley CM, Stripp BR 2001. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am. J. Respir. Cell Mol. Biol. 24:6671–81
     [Google Scholar]
  49. 49. 
    Giangreco A, Reynolds SD, Stripp BR 2002. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am. J. Pathol. 161:1173–82
     [Google Scholar]
  50. 50. 
    Peake JL, Reynolds SD, Stripp BR, Stephens KE, Pinkerton KE 2000. Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury. Am. J. Pathol. 156:1279–86
     [Google Scholar]
  51. 51. 
    Morimoto M, Nishinakamura R, Saga Y, Kopan R 2012. Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development 139:234365–73
     [Google Scholar]
  52. 52. 
    Volckaert T, Dill E, Campbell A, Tiozzo C, Majka S et al. 2011. Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury. J. Clin. Investig. 121:114409–19
     [Google Scholar]
  53. 53. 
    Giangreco A, Arwert EN, Rosewell IR, Snyder J, Watt FM, Stripp BR 2009. Stem cells are dispensable for lung homeostasis but restore airways after injury. PNAS 106:239286–91
     [Google Scholar]
  54. 54. 
    Song H, Yao E, Lin C, Gacayan R, Chen M-H, Chuang P-T 2012. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis. PNAS 109:4317531–36
     [Google Scholar]
  55. 55. 
    Ouadah Y, Rojas ER, Riordan DP, Capostagno S, Kuo CS, Krasnow MA 2019. Rare pulmonary neuroendocrine cells are stem cells regulated by Rb, p53, and Notch. Cell 179:2403–23
     [Google Scholar]
  56. 56. 
    Kim CFB, Jackson EL, Woolfenden AE, Lawrence S, Babar I et al. 2005. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:6823–35
     [Google Scholar]
  57. 57. 
    Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR et al. 2011. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. PNAS 108:52E1475–83
     [Google Scholar]
  58. 58. 
    Zheng D, Limmon GV, Yin L, Leung NHN, Yu H et al. 2012. Regeneration of alveolar type I and II cells from Scgb1a1-expressing cells following severe pulmonary damage induced by bleomycin and influenza. PLOS ONE 7:10e48451
     [Google Scholar]
  59. 59. 
    Salwig I, Spitznagel B, Vazquez Armendariz AI, Khalooghi K, Guenther S et al. 2019. Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo. . EMBO J 38:12e102099
     [Google Scholar]
  60. 60. 
    Liu Q, Liu K, Cui G, Huang X, Yao S et al. 2019. Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction. Nat. Genet. 51:4728–38
     [Google Scholar]
  61. 61. 
    Basil MC, Morrisey EE. 2019. BASC‐ing in the glow: bronchioalveolar stem cells get their place in the lung. EMBO J 38:12e102344
     [Google Scholar]
  62. 62. 
    Mason RJ, Williams MC. 1977. Type II alveolar cell. Defender of the alveolus. Am. Rev. Respir. Dis. 115:6 Part 281–91
     [Google Scholar]
  63. 63. 
    Bowden DH, Davies E, Wyatt JP 1968. Cytodynamics of pulmonary alveolar cells in the mouse. Arch. Pathol. 86:6667–70
     [Google Scholar]
  64. 64. 
    Adamson IY, Bowden DH, Wyatt JP 1970. Oxygen poisoning in mice. Ultrastructural and surfactant studies during exposure and recovery. Arch. Pathol. 90:5463–72
     [Google Scholar]
  65. 65. 
    Adamson IY, Bowden DH. 1974. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab. Investig. 30:135–42
     [Google Scholar]
  66. 66. 
    Adamson IY, Bowden DH. 1975. Derivation of type 1 epithelium from type 2 cells in the developing rat lung. Lab. Investig. 32:6736–45
     [Google Scholar]
  67. 67. 
    Perl AKT, Wert SE, Nagy A, Lobe CG, Whitsett JA 2002. Early restriction of peripheral and proximal cell lineages during formation of the lung. PNAS 99:1610482–87
     [Google Scholar]
  68. 68. 
    Evans MJ, Cabral LJ, Stephens RJ, Freeman G 1975. Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2. Exp. Mol. Pathol. 22:1142–50
     [Google Scholar]
  69. 69. 
    Barkauskas CE, Cronce MJ, Rackley CR, Bowie EJ, Keene DR et al. 2013. Type 2 alveolar cells are stem cells in adult lung. J. Clin. Investig. 123:73025–36
     [Google Scholar]
  70. 70. 
    Desai TJ, Brownfield DG, Krasnow MA 2014. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507:7491190–94
     [Google Scholar]
  71. 71. 
    Nabhan AN, Brownfield DG, Harbury PB, Krasnow MA, Desai TJ 2018. Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 359:63801118–23
     [Google Scholar]
  72. 72. 
    Zacharias WJ, Frank DB, Zepp JA, Morley MP, Alkhaleel FA et al. 2018. Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature 555:7695251–55
     [Google Scholar]
  73. 73. 
    Frank DB, Peng T, Zepp JA, Snitow M, Vincent TL et al. 2016. Emergence of a wave of Wnt signaling that regulates lung alveologenesis by controlling epithelial self-renewal and differentiation. Cell Rep 17:92312–25
     [Google Scholar]
  74. 74. 
    Laughney AM, Hu J, Campbell NR, Bakhoum SF, Setty M et al. 2020. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nat. Med. 26:2259–69
     [Google Scholar]
  75. 75. 
    Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC et al. 2018. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 199:121517–36
     [Google Scholar]
  76. 76. 
    Weibel ER. 2015. On the tricks alveolar epithelial cells play to make a good lung. Am. J. Respir. Crit. Care Med. 191:5504–13
     [Google Scholar]
  77. 77. 
    Gonzalez RF, Allen L, Dobbs LG 2009. Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol. 297:6L1045–55
     [Google Scholar]
  78. 78. 
    Borok Z, Crandall ED. 2009. More life for a “terminal” cell. Am. J. Physiol. Lung Cell. Mol. Physiol. 297:6L1042–44
     [Google Scholar]
  79. 79. 
    Wang S, Hubmayr RD. 2012. Type I alveolar epithelial phenotype in primary culture. Am. J. Respir. Cell Mol. Biol. 44:5692–99
     [Google Scholar]
  80. 80. 
    Jain R, Barkauskas CE, Takeda N, Bowie EJ, Aghajanian H et al. 2015. Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung. Nat. Commun. 6:6727
     [Google Scholar]
  81. 81. 
    Xu Y, Mizuno T, Sridharan A, Du Y, Guo M et al. 2017. Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis. JCI Insight 1:20e90558
     [Google Scholar]
  82. 82. 
    Chung M-I, Hogan BLM. 2018. Ager-CreERT2: a new genetic tool for studying lung alveolar development, homeostasis, and repair. Am. J. Respir. Cell Mol. Biol. 59:6706–12
     [Google Scholar]
  83. 83. 
    Chung M-I, Bujnis M, Barkauskas CE, Kobayashi Y, Hogan BLM 2018. Niche-mediated BMP/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation. Development 145:9dev163014
     [Google Scholar]
  84. 84. 
    Kumar PA, Hu Y, Yamamoto Y, Hoe NB, Wei TS et al. 2011. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell 147:3525–38
     [Google Scholar]
  85. 85. 
    Xi Y, Kim T, Brumwell AN, Driver IH, Wei Y et al. 2017. Local lung hypoxia determines epithelial fate decisions during alveolar regeneration. Nat. Cell Biol. 19:8904–14
     [Google Scholar]
  86. 86. 
    Yang Y, Riccio P, Schotsaert M, Mori M, Lu J et al. 2018. Spatial-temporal lineage restrictions of embryonic p63+ progenitors establish distinct stem cell pools in adult airways. Dev. Cell. 44:6752–54
     [Google Scholar]
  87. 87. 
    Kathiriya JJ, Brumwell AN, Jackson JR, Tang X, Chapman HA 2020. Distinct airway epithelial stem cells hide among club cells but mobilize to promote alveolar regeneration. Cell Stem Cell 26:3346–58
     [Google Scholar]
  88. 88. 
    Chapman HA, Li X, Alexander JP, Brumwell A, Lorizio W et al. 2011. Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice. J. Clin. Investig. 121:72855–62
     [Google Scholar]
  89. 89. 
    Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG et al. 2014. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 517:7536621–25
     [Google Scholar]
  90. 90. 
    Raven A, Lu W-Y, Man TY, Ferreira-Gonzalez S, O'Duibhir E et al. 2017. Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547:7663350–54
     [Google Scholar]
  91. 91. 
    Russell JO, Lu W-Y, Okabe H, Abrams M, Oertel M et al. 2019. Hepatocyte-specific β-catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes. Hepatology 69:2742–59
     [Google Scholar]
  92. 92. 
    Deng X, Zhang X, Li W, Feng R-X, Li L et al. 2018. Chronic liver injury induces conversion of biliary epithelial cells into hepatocytes. Cell Stem Cell 23:1114–22
     [Google Scholar]
  93. 93. 
    Manco R, Clerbaux L-A, Verhulst S, Bou Nader M, Sempoux C et al. 2019. Reactive cholangiocytes differentiate into proliferative hepatocytes with efficient DNA repair in mice with chronic liver injury. J. Hepatol. 70:61180–91
     [Google Scholar]
  94. 94. 
    Ding B-S, Nolan DJ, Guo P, Babazadeh AO, Cao Z et al. 2011. Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. Cell 147:3539–53
     [Google Scholar]
  95. 95. 
    Lechner AJ, Driver IH, Lee J, Conroy CM, Nagle A et al. 2017. Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy. Cell Stem Cell 21:1120–27
     [Google Scholar]
  96. 96. 
    Perl AKT, Gale E. 2009. FGF signaling is required for myofibroblast differentiation during alveolar regeneration. Am. J. Physiol. Lung Cell. Mol. Physiol. 297:2L299–308
     [Google Scholar]
  97. 97. 
    Chen L, Acciani T, Le Cras T, Lutzko C, Perl AKT 2012. Dynamic regulation of platelet-derived growth factor receptor α expression in alveolar fibroblasts during realveolarization. Am. J. Respir. Cell Mol. Biol. 47:4517–27
     [Google Scholar]
  98. 98. 
    Endale M, Ahlfeld S, Bao E, Chen X, Green J et al. 2017. Temporal, spatial, and phenotypical changes of PDGFRα expressing fibroblasts during late lung development. Dev. Biol. 425:2161–75
     [Google Scholar]
  99. 99. 
    Zepp JA, Zacharias WJ, Frank DB, Cavanaugh CA, Zhou S et al. 2017. Distinct mesenchymal lineages and niches promote epithelial self-renewal and myofibrogenesis in the lung. Cell 170:61134–48
     [Google Scholar]
  100. 100. 
    Lee J-H, Tammela T, Hofree M, Choi J, Marjanovic ND et al. 2017. Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6. Cell 170:61149–63
     [Google Scholar]
  101. 101. 
    Sirianni FE, Chu FSF, Walker DC 2003. Human alveolar wall fibroblasts directly link epithelial type 2 cells to capillary endothelium. Am. J. Respir. Crit. Care Med. 168:121532–37
     [Google Scholar]
  102. 102. 
    Gehr P, Bachofen M, Weibel ER 1978. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir. Physiol. 32:2121–40
     [Google Scholar]
  103. 103. 
    Knust J, Ochs M, Gundersen HJG, Nyengaard JR 2009. Stereological estimates of alveolar number and size and capillary length and surface area in mice lungs. Anat. Rec. 292:1113–22
     [Google Scholar]
  104. 104. 
    Rock JR, Randell SH, Hogan BLM 2010. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis. Model. Mech. 3:9–10545–56
     [Google Scholar]
  105. 105. 
    Rackley CR, Stripp BR. 2012. Building and maintaining the epithelium of the lung. J. Clin. Investig. 122:82724–30
     [Google Scholar]
  106. 106. 
    Holmes C, Stanford WL. 2007. Concise review: stem cell antigen-1: expression, function, and enigma. Stem Cells 25:61339–47
     [Google Scholar]
  107. 107. 
    Dor Y, Brown J, Martinez OI, Melton DA 2004. Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:698741–46
     [Google Scholar]
  108. 108. 
    Wang D, Wang J, Bai L, Pan H, Feng H et al. 2020. Long-term expansion of pancreatic islet organoids from resident Procr+ progenitors. Cell 180:61198–211
     [Google Scholar]
  109. 109. 
    Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M et al. 2004. Development of definitive endoderm from embryonic stem cells in culture. Development 131:71651–62
     [Google Scholar]
  110. 110. 
    Green MD, Chen A, Nostro M-C, d'Souza SL, Schaniel C et al. 2011. Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nat. Biotechnol. 29:3267–72
     [Google Scholar]
  111. 111. 
    Longmire TA, Ikonomou L, Hawkins F, Christodoulou C, Cao Y et al. 2012. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 10:4398–411
     [Google Scholar]
  112. 112. 
    Mou H, Zhao R, Sherwood R, Ahfeldt T, Lapey A et al. 2012. Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell Stem Cell 10:4385–97
     [Google Scholar]
  113. 113. 
    Dye BR, Hill DR, Ferguson MAH, Tsai Y-H, Nagy MS et al. 2015. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 4:1999
     [Google Scholar]
  114. 114. 
    Rankin SA, Han L, McCracken KW, Kenny AP, Anglin CT et al. 2016. A retinoic acid-hedgehog cascade coordinates mesoderm-inducing signals and endoderm competence during lung specification. Cell Rep 16:166–78
     [Google Scholar]
  115. 115. 
    Huang SXL, Islam MN, O'Neill J, Hu Z, Yang Y-G et al. 2014. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat. Biotechnol. 32:184–91
     [Google Scholar]
  116. 116. 
    Serra M, Alysandratos K-D, Hawkins F, McCauley KB, Jacob A et al. 2017. Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification. Development 144:213879–93
     [Google Scholar]
  117. 117. 
    Ikonomou L, Herriges MJ, Lewandowski SL, Marsland R, Villacorta-Martin C et al. 2020. The in vivo genetic program of murine primordial lung epithelial progenitors. Nat. Commun. 11:1635–17
     [Google Scholar]
  118. 118. 
    Jacob A, Morley M, Hawkins F, McCauley KB, Jean JC et al. 2017. Differentiation of human pluripotent stem cells into functional lung alveolar epithelial cells. Cell Stem Cell 21:4472–88
     [Google Scholar]
  119. 119. 
    Yamamoto Y, Gotoh S, Korogi Y, Seki M, Konishi S et al. 2017. Long-term expansion of alveolar stem cells derived from human iPS cells in organoids. Nat. Methods 14:111097–106
     [Google Scholar]
  120. 120. 
    Jacob A, Vedaie M, Roberts DA, Thomas DC, Villacorta-Martin C et al. 2019. Derivation of self-renewing lung alveolar epithelial type II cells from human pluripotent stem cells. Nat. Protoc. 14:123303–32
     [Google Scholar]
  121. 121. 
    Konishi S, Gotoh S, Tateishi K, Yamamoto Y, Korogi Y et al. 2016. Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Rep 6:118–25
     [Google Scholar]
  122. 122. 
    McCauley KB, Hawkins F, Serra M, Thomas DC, Jacob A, Kotton DN 2017. Efficient derivation of functional human airway epithelium from pluripotent stem cells via temporal regulation of Wnt signaling. Cell Stem Cell 20:6844–46
     [Google Scholar]
  123. 123. 
    Hawkins FJ, Suzuki S, Beermann ML, Barillà C, Wang R et al. 2020. Derivation of airway basal stem cells from human pluripotent stem cells. Cell Stem Cell In press
    [Google Scholar]
  124. 124. 
    Huang SXL, Green MD, de Carvalho AT, Mumau M, Chen Y-W et al. 2015. The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells. Nat. Protoc. 10:3413–25
     [Google Scholar]
  125. 125. 
    de Carvalho ALRT, Strikoudis A, Liu H-Y, Chen Y-W, Dantas TJ et al. 2019. Glycogen synthase kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture. Development 146:2dev171652
     [Google Scholar]
  126. 126. 
    Gotoh S, Ito I, Nagasaki T, Yamamoto Y, Konishi S et al. 2014. Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells. Stem Cell Rep 3:3394–403
     [Google Scholar]
  127. 127. 
    Hawkins F, Kramer P, Jacob A, Driver I, Thomas DC et al. 2017. Prospective isolation of NKX2–1-expressing human lung progenitors derived from pluripotent stem cells. J. Clin. Investig. 127:62277–94
     [Google Scholar]
  128. 128. 
    Korogi Y, Gotoh S, Ikeo S, Yamamoto Y, Sone N et al. 2019. In vitro disease modeling of Hermansky-Pudlak syndrome type 2 using human induced pluripotent stem cell-derived alveolar organoids. Stem Cell Rep 12:3431–40
     [Google Scholar]
  129. 129. 
    Hurley K, Ding J, Villacorta-Martin C, Herriges MJ, Jacob A et al. 2020. Reconstructed single-cell fate trajectories define lineage plasticity windows during differentiation of human PSC-derived distal lung progenitors. Cell Stem Cell 16:4593–608
     [Google Scholar]
  130. 130. 
    Chen Y-W, Huang SX, de Carvalho ALRT, Ho S-H, Islam MN et al. 2017. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat. Cell Biol. 19:5542–49
     [Google Scholar]
  131. 131. 
    Dye BR, Dedhia PH, Miller AJ, Nagy MS, White ES et al. 2016. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. eLife 5:e19732
     [Google Scholar]
  132. 132. 
    Miller AJ, Hill DR, Nagy MS, Aoki Y, Dye BR et al. 2018. In vitro induction and in vivo engraftment of lung bud tip progenitor cells derived from human pluripotent stem cells. Stem Cell Rep 10:1101–19
     [Google Scholar]
  133. 133. 
    Miller AJ, Dye BR, Ferrer-Torres D, Hill DR, Overeem AW et al. 2019. Generation of lung organoids from human pluripotent stem cells in vitro. Nat. Protoc. 14:2518–40
     [Google Scholar]
  134. 134. 
    Rosen C, Shezen E, Aronovich A, Klionsky YZ, Yaakov Y et al. 2015. Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice. Nat. Med. 21:8869–79
     [Google Scholar]
  135. 135. 
    Nichane M, Javed A, Sivakamasundari V, Ganesan M, Ang LT et al. 2017. Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors. Nat. Methods 14:121205–12
     [Google Scholar]
  136. 136. 
    Farrow N, Cmielewski P, Donnelley M, Rout-Pitt N, Moodley Y et al. 2018. Epithelial disruption: a new paradigm enabling human airway stem cell transplantation. Stem Cell Res. Ther. 9:1277–78
     [Google Scholar]
  137. 137. 
    Krentsis IM, Rosen C, Shezen E, Aronovich A, Nathanson B et al. 2018. Lung injury repair by transplantation of adult lung cells following preconditioning of recipient mice. Stem Cells Transl. Med. 7:168–77
     [Google Scholar]
  138. 138. 
    Hillel-Karniel C, Rosen C, Milman-Krentsis I, Orgad R, Bachar-Lustig E et al. 2020. Multi-lineage lung regeneration by stem cell transplantation across major genetic barriers. Cell Rep 30:3807–19
     [Google Scholar]
  139. 139. 
    Weiner AI, Jackson SR, Zhao G, Quansah KK, Farshchian JN et al. 2019. Mesenchyme-free expansion and transplantation of adult alveolar progenitor cells: steps toward cell-based regenerative therapies. NPJ Regen. Med. 4:17
     [Google Scholar]
  140. 140. 
    Kotton DN, Fabian AJ, Mulligan RC 2005. Failure of bone marrow to reconstitute lung epithelium. Am. J. Respir. Cell Mol. Biol. 33:4328–34
     [Google Scholar]
  141. 141. 
    Kotton DN. 2012. Next-generation regeneration. Am. J. Respir. Crit. Care Med. 185:121255–60
     [Google Scholar]
  142. 142. 
    Sipp D, Robey PG, Turner L 2018. Clear up this stem-cell mess. Nature 561:7724455–57
     [Google Scholar]
  143. 143. 
    Ikonomou L, Freishtat RJ, Wagner DE, Panoskaltsis-Mortari A, Weiss DJ 2016. The global emergence of unregulated stem cell treatments for respiratory diseases. Professional societies need to act. Ann. Am. Thorac. Soc. 13:81205–7
     [Google Scholar]
  144. 144. 
    Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG et al. 2013. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat. Med. 19:135–42
     [Google Scholar]
  145. 145. 
    Robey PG. 2017. “Mesenchymal stem cells”: fact or fiction, and implications in their therapeutic use. F1000Research 6:524–28
     [Google Scholar]
  146. 146. 
    Ikonomou L, Wagner DE, Turner L, Weiss DJ 2019. Translating basic research into safe and effective cell-based treatments for respiratory diseases. Ann. Am. Thorac. Soc. 16:6657–68
     [Google Scholar]
  147. 147. 
    Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I et al. 2010. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16:8927–33
     [Google Scholar]
  148. 148. 
    Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L et al. 2010. Tissue-engineered lungs for in vivo implantation. Science 329:5991538–41
     [Google Scholar]
  149. 149. 
    Dorrello NV, Guenthart BA, O'Neill JD, Kim J, Cunningham K et al. 2017. Functional vascularized lung grafts for lung bioengineering. Sci. Adv. 3:8e1700521
     [Google Scholar]
  150. 150. 
    Dutta D, Heo I, Clevers H 2017. Disease modeling in stem cell-derived 3D organoid systems. Trends Mol. Med. 23:5393–410
     [Google Scholar]
  151. 151. 
    Flodby P, Borok Z, Banfalvi A, Zhou B, Gao D et al. 2010. Directed expression of Cre in alveolar epithelial type 1 cells. Am. J. Respir. Cell Mol. Biol. 43:2173–78
     [Google Scholar]
/content/journals/10.1146/annurev-physiol-041520-092904
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Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration
Annual Review of Physiology 83, 529 (2021); https://doi.org/10.1146/annurev-physiol-041520-092904
/content/journals/10.1146/annurev-physiol-041520-092904
/content/journals/10.1146/annurev-physiol-041520-092904
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