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A Maverick Review of Common Stem/Progenitor Markers in Lung Development

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Abstract

Several attempts have been made to reconstruct the whole lung using pluripotent stem cells (PSCs) to treat terminal stage diseases, such as chronic obstructive pulmonary disease [COPD] and idiopathic pulmonary fibrosis [IPF], for which whole-organ transplantation is currently the only treatment option. The development of induced differentiation technologies has made it possible to regenerate lungs from the ‘bottom-up’ via stepwise protocols. Nonetheless, the earliest lung multipotent progenitors, namely lung primordial stem cells, have not been identified to date. Considering the intricate crosstalk network that regulates lung development, stepwise protocols to differentiate PSCs into lung progenitors have raised some key questions: (1) the heterogeneity of these induced progenitors, and (2) obtaining a high-purity population. One important strategy to overcome these hurdles is to identify relevant markers or factors that regulate the complex network in lung morphogenesis according to those erected in vivo and ex vivo experiments. For screening lung primordial stem cells, several markers are ‘on the shelf’, and this review explores the most common or substantiated candidates. We artificially divided these markers into positive selecting and negative limiting proximal or distal markers as well as early progenitor markers that can be used to identify lung primordial stem cell, which represents the earliest progenitor during lung morphogenesis.

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References

  1. Kotton, D. N., & Morrisey, E. E. (2014). Lung regeneration: Mechanisms, applications and emerging stem cell populations. Nature Medicine, 20(8), 822–832.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Kumar, V. H., et al. (2005). Growth factors in lung development. Advances in Clinical Chemistry, 40, 261–316.

    CAS  PubMed  Google Scholar 

  3. Schittny, J. C. (2017). Development of the lung. Cell and Tissue Research, 367(3), 427–444.

    PubMed  PubMed Central  Google Scholar 

  4. Morrisey, E. E., & Hogan, B. L. (2010). Preparing for the first breath: Genetic and cellular mechanisms in lung development. Developmental Cell, 18(1), 8–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Rankin, S. A., & Zorn, A. M. (2014). Gene regulatory networks governing lung specification. Journal of Cellular Biochemistry, 115(8), 1343–1350.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bilodeau, C., et al. (2021). TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds. NPJ Regenerative Medicine, 6(1), 12.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Vaughan, A. E., et al. (2015). Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature, 517(7536), 621–625.

    CAS  PubMed  Google Scholar 

  8. Shojaie, S., et al. (2015). Acellular lung scaffolds direct differentiation of endoderm to functional airway epithelial cells: Requirement of matrix-bound HS proteoglycans. Stem Cell Reports, 4(3), 419–430.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Inanlou, M. R., Baguma-Nibasheka, M., & Kablar, B. (2005). The role of fetal breathing-like movements in lung organogenesis. Histology and Histopathology, 20(4), 1261–1266.

    CAS  PubMed  Google Scholar 

  10. Li, J., et al. (2018). The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells. Developmental Cell, 44(3), 297-312.e5.

    CAS  PubMed  Google Scholar 

  11. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

    CAS  PubMed  Google Scholar 

  12. Hawkins, F., & Kotton, D. N. (2015). Embryonic and Induced Pluripotent Stem Cells for Lung Regeneration. Annals of the American Thoracic Society, 12(Supplement 1), S50–S53.

    PubMed  Google Scholar 

  13. Ikonomou, L., & Kotton, D. N. (2015). Derivation of Endodermal Progenitors From Pluripotent Stem Cells. Journal of Cellular Physiology, 230(2), 246–258.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Calvert, B.A., Ryan Firth, A.L. (2020). Application of iPSC to Modelling of Respiratory Diseases. Advances in Experimental Medicine and Biology, 1237, 1–16.

  15. Duchesneau, P., Waddell, T. K., Karoubi, G. (2020). Cell-Based Therapeutic Approaches for Cystic Fibrosis. International Journal of Molecular Sciences, 21(15):5219.

  16. Tavakol, D. N., Fleischer, S., & Vunjak-Novakovic, G. (2021). Harnessing organs-on-a-chip to model tissue regeneration. Cell Stem Cell, 28(6), 993–1015.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Parekh, K., et al. (2020). Stem cells and lung regeneration. American journal of physiology. Cell physiology, 319(4), C675–C693.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Basil, M. C., et al. (2020). The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future. Cell Stem Cell, 26(4), 482–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Nichane, M., et al. (2017). Isolation and 3D expansion of multipotent Sox9(+) mouse lung progenitors. Nature Methods, 14(12), 1205–1212.

    CAS  PubMed  Google Scholar 

  20. Yang, Y., et al. (2018). Spatial-Temporal Lineage Restrictions of Embryonic p63(+) Progenitors Establish Distinct Stem Cell Pools in Adult Airways. Developmental Cell, 44(6), 752-761.e4.

    PubMed  PubMed Central  Google Scholar 

  21. Hawkins, F., et al. (2017). Prospective isolation of NKX2-1-expressing human lung progenitors derived from pluripotent stem cells. The Journal of Clinical Investigation, 127(6), 2277–2294.

    PubMed  PubMed Central  Google Scholar 

  22. Xi, Y., et al. (2017). Local lung hypoxia determines epithelial fate decisions during alveolar regeneration. Nature Cell Biology, 19(8), 904–914.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim, C. F., et al. (2005). Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 121(6), 823–835.

    CAS  PubMed  Google Scholar 

  24. Liu, Q., et al. (2019). Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction. Nature Genetics, 51(4), 728–738.

    CAS  PubMed  Google Scholar 

  25. Salwig, I., et al. (2019). Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo. Embo Journal, 38(12):e102099.

  26. Havrilak, J. A., Melton, K. R., & Shannon, J. M. (2017). Endothelial cells are not required for specification of respiratory progenitors. Developmental Biology, 427(1), 93–105.

    CAS  PubMed  Google Scholar 

  27. Ray, S., et al. (2016). Rare SOX2(+) Airway Progenitor Cells Generate KRT5(+) Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection. Stem Cell Reports, 7(5), 817–825.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Herriges, J. C., et al. (2012). Genome-scale study of transcription factor expression in the branching mouse lung. Developmental Dynamics, 241(9), 1432–1453.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Que, J., et al. (2007). Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development, 134(13), 2521–2531.

    CAS  PubMed  Google Scholar 

  30. Tsao, P. N., et al. (2009). Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development, 136(13), 2297–2307.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Tompkins, D. H., et al. (2011). Sox2 activates cell proliferation and differentiation in the respiratory epithelium. American Journal of Respiratory Cell and Molecular Biology, 45(1), 101–110.

    CAS  PubMed  Google Scholar 

  32. Que, J., et al. (2009). Multiple roles for Sox2 in the developing and adult mouse trachea. Development, 136(11), 1899–1907.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen, X., Vega, V. B., & Ng, H. H. (2008). Transcriptional regulatory networks in embryonic stem cells. Cold Spring Harbor Symposia on Quantitative Biology, 73, 203–209.

    CAS  PubMed  Google Scholar 

  34. Bhattacharya, S., et al. (2019). SOX2 Regulates P63 and Stem/Progenitor Cell State in the Corneal Epithelium. Stem Cells, 37(3), 417–429.

    CAS  PubMed  Google Scholar 

  35. Nikolić, M.Z., et al. (2017). Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids. Elife, 6:e26575.

  36. Alanis, D. M., et al. (2014). Two nested developmental waves demarcate a compartment boundary in the mouse lung. Nature Communications, 5, 3923.

    PubMed  Google Scholar 

  37. Han, L., et al. (2020). Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis. Nature Communications, 11(1), 4158.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Yang, A., et al. (1998). p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Molecular Cell, 2(3), 305–316.

    CAS  PubMed  Google Scholar 

  39. Koster, M. I. (2010). p63 in skin development and ectodermal dysplasias. The Journal of Investigative Dermatology, 130(10), 2352–2358.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Thompson, C. A., DeLaForest, A., & Battle, M. A. (2018). Patterning the gastrointestinal epithelium to confer regional-specific functions. Developmental Biology, 435(2), 97–108.

    CAS  PubMed  Google Scholar 

  41. Evans, M. J., et al. (2001). Cellular and molecular characteristics of basal cells in airway epithelium. Experimental Lung Research, 27(5), 401–415.

    CAS  PubMed  Google Scholar 

  42. Arason, A. J., et al. (2014). deltaNp63 has a role in maintaining epithelial integrity in airway epithelium. PLoS ONE, 9(2), e88683.

    PubMed  PubMed Central  Google Scholar 

  43. Daniely, Y., et al. (2004). Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium. American Journal of Physiology. Cell Physiology, 287(1), C171–C181.

    CAS  PubMed  Google Scholar 

  44. Rock, J. R., Randell, S. H., & Hogan, B. L. (2010). Airway basal stem cells: A perspective on their roles in epithelial homeostasis and remodeling. Disease Models & Mechanisms, 3(9–10), 545–556.

    CAS  Google Scholar 

  45. Rock, J. R., & Hogan, B. L. (2010). Developmental biology. Branching takes nerve. Science, 329(5999), 1610–1611.

    CAS  PubMed  Google Scholar 

  46. Romano, R. A., et al. (2009). An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS ONE, 4(5), e5623.

    PubMed  PubMed Central  Google Scholar 

  47. Hutton, E., et al. (1998). Functional differences between keratins of stratified and simple epithelia. Journal of Cell Biology, 143(2), 487–499.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Zuo, W., et al. (2015). p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature, 517(7536), 616–620.

    CAS  PubMed  Google Scholar 

  49. Wang, X., et al. (2021). Intrapulmonary distal airway stem cell transplantation repairs lung injury in chronic obstructive pulmonary disease. Cell Proliferation, 54(6), e13046.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Cole, B. B., et al. (2010). Tracheal Basal cells: A facultative progenitor cell pool. American Journal of Pathology, 177(1), 362–376.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang, J., et al. (2016). The development and plasticity of alveolar type 1 cells. Development, 143(1), 54–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Ghosh, M., et al. (2011). Context-dependent differentiation of multipotential keratin 14-expressing tracheal basal cells. American Journal of Respiratory Cell and Molecular Biology, 45(2), 403–410.

    CAS  PubMed  Google Scholar 

  53. Smirnova, N. F., et al. (2016). Detection and quantification of epithelial progenitor cell populations in human healthy and IPF lungs. Respiratory Research, 17(1), 83.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Ryerse, J. S., et al. (2001). Immunolocalization of CC10 in Clara cells in mouse and human lung. Histochemistry and Cell Biology, 115(4), 325–332.

    CAS  PubMed  Google Scholar 

  55. Liu, K., et al. (2020). Triple-cell lineage tracing by a dual reporter on a single allele. Journal of Biological Chemistry, 295(3), 690–700.

    PubMed  Google Scholar 

  56. Zheng, D., et al. (2013). A cellular pathway involved in Clara cell to alveolar type II cell differentiation after severe lung injury. PLoS ONE, 8(8), e71028.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Reynolds, S. D., et al. (2000). Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. American Journal of Pathology, 156(1), 269–278.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Rawlins, E. L., 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(6), 525–534.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Zheng, D., Yin, L., & Chen, J. (2014). Evidence for Scgb1a1(+) cells in the generation of p63(+) cells in the damaged lung parenchyma. American Journal of Respiratory Cell and Molecular Biology, 50(3), 595–604.

    PubMed  Google Scholar 

  60. Serls, A. E., et al. (2005). Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development, 132(1), 35–47.

    CAS  PubMed  Google Scholar 

  61. Xu, P., et al. (1998). Morphometric analysis of the immunohistochemical expression of Clara cell 10-kDa protein and surfactant apoproteins A and B in the developing bronchi and bronchioles of human fetuses and neonates. Virchows Archiv, 432(1), 17–25.

    CAS  PubMed  Google Scholar 

  62. Tompkins, D. H., et al. (2009). Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells. PLoS ONE, 4(12), e8248.

    PubMed  PubMed Central  Google Scholar 

  63. Elluru, R. G., & Whitsett, J. A. (2004). Potential role of Sox9 in patterning tracheal cartilage ring formation in an embryonic mouse model. Archives of Otolaryngology - Head and Neck Surgery, 130(6), 732–736.

    PubMed  Google Scholar 

  64. Wright, E., et al. (1995). The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos. Nature Genetics, 9(1), 15–20.

    CAS  PubMed  Google Scholar 

  65. Rockich, B. E., et al. (2013). Sox9 plays multiple roles in the lung epithelium during branching morphogenesis. Proceedings of the National Academy of Sciences of the United States of America, 110(47), E4456–E4464.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Bi, W., et al. (2001). Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization. Proceedings of the National Academy of Sciences of the United States of America, 98(12), 6698–6703.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Perl, A. K., et al. (2005). Normal lung development and function after Sox9 inactivation in the respiratory epithelium. Genesis, 41(1), 23–32.

    CAS  PubMed  Google Scholar 

  68. Turcatel, G., et al. (2013). Lung mesenchymal expression of Sox9 plays a critical role in tracheal development. BMC Biology, 11, 117.

    PubMed  PubMed Central  Google Scholar 

  69. Li, L., et al. (2021). SOX9 inactivation affects the proliferation and differentiation of human lung organoids. Stem Cell Research & Therapy, 12(1), 343.

    CAS  Google Scholar 

  70. Ma, Q., et al. (2018). Regeneration of functional alveoli by adult human SOX9(+) airway basal cell transplantation. Protein & Cell, 9(3), 267–282.

    CAS  Google Scholar 

  71. Kathiriya, J. J., et al. (2020). Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration. Cell Stem Cell, 26(3), 346-358.e4.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Barkauskas, C. E., et al. (2013). Type 2 alveolar cells are stem cells in adult lung. The Journal of Clinical Investigation, 123(7), 3025–3036.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Wert, S. E., et al. (1993). Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice. Developmental Biology, 156(2), 426–443.

    CAS  PubMed  Google Scholar 

  74. Laresgoiti, U., et al. (2016). Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate. Development, 143(20), 3686–3699.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Liebler, J. M., et al. (2016). Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung. American Journal of Physiology. Lung Cellular and Molecular Physiology, 310(2), L114–L120.

    PubMed  Google Scholar 

  76. Glasser, S. W., et al. (2001). Altered stability of pulmonary surfactant in SP-C-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 98(11), 6366–6371.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Rock, J. R., et al. (2011). Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America, 108(52), E1475–E1483.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Gonzalez, R., et al. (2019). Cell fate analysis in fetal mouse lung reveals distinct pathways for TI and TII cell development. American Journal of Physiology. Lung Cellular and Molecular Physiology, 317(5), L653-l666.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Treutlein, B., et al. (2014). Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature, 509(7500), 371–375.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Jain, R., et al. (2015). Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nature Communications, 6, 6727.

    CAS  PubMed  Google Scholar 

  81. Yin, Z., et al. (2006). Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression. American Journal of Physiology. Lung Cellular and Molecular Physiology, 291(2), L191–9

  82. Ota, C., et al. (2018). Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis. Science and Reports, 8(1), 12983.

    Google Scholar 

  83. Stahlman, M. T., Gray, M. E., & Whitsett, J. A. (1996). Expression of thyroid transcription factor-1(TTF-1) in fetal and neonatal human lung. Journal of Histochemistry and Cytochemistry, 44(7), 673–678.

    CAS  PubMed  Google Scholar 

  84. Rankin, S. A., et al. (2018). Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis. Developmental Biology, 434(1), 121–132.

    CAS  PubMed  Google Scholar 

  85. Minoo, P., et al. (1999). Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos. Developmental Biology, 209(1), 60–71.

  86. Li, E., et al. (2021). Blastocyst complementation reveals that NKX2-1 establishes the proximal-peripheral boundary of the airway epithelium. Developmental Dynamics, 250(7), 1001–1020.

    CAS  PubMed  Google Scholar 

  87. Kimura, S., et al. (1996). The T/ebp null mouse: Thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes & Development, 10(1), 60–69.

    CAS  Google Scholar 

  88. Wert, S. E., et al. (2002). Increased expression of thyroid transcription factor-1 (TTF-1) in respiratory epithelial cells inhibits alveolarization and causes pulmonary inflammation. Developmental Biology, 242(2), 75–87.

    CAS  PubMed  Google Scholar 

  89. Little, D. R., et al. (2019). Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2–1. Proceedings of the National Academy of Sciences of the United States of America, 116(41), 20545–20555.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Little, D. R., et al. (2021). Differential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo. Nature Communications, 12(1), 2509.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Goh, K. J., et al. (2021). An NKX2-1(GFP) and TP63(tdTomato) dual fluorescent reporter for the investigation of human lung basal cell biology. Science and Reports, 11(1), 4712.

    CAS  Google Scholar 

  92. Hawkins, F. J., et al. (2021). Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells. Cell Stem Cell, 28(1), 79-95.e8.

    CAS  PubMed  Google Scholar 

  93. Bilodeau, M., et al. (2014). Identification of a proximal progenitor population from murine fetal lungs with clonogenic and multilineage differentiation potential. Stem Cell Reports, 3(4), 634–649.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Song, H., et al. (2012). Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17531–17536.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Yao, E., et al. (2018). Notch Signaling Controls Transdifferentiation of Pulmonary Neuroendocrine Cells in Response to Lung Injury. Stem Cells, 36(3), 377–391.

    CAS  PubMed  Google Scholar 

  96. Tanaka, Y., et al. (2018). Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung. Experimental Cell Research, 372(2), 141–149.

    CAS  PubMed  Google Scholar 

  97. Ang, S. L., et al. (1993). The formation and maintenance of the definitive endoderm lineage in the mouse: Involvement of HNF3/forkhead proteins. Development, 119(4), 1301–1315.

    CAS  PubMed  Google Scholar 

  98. Monaghan, A. P., et al. (1993). Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development, 119(3), 567–578.

    CAS  PubMed  Google Scholar 

  99. Wan, H., et al. (2005). Compensatory roles of Foxa1 and Foxa2 during lung morphogenesis. Journal of Biological Chemistry, 280(14), 13809–13816.

    CAS  PubMed  Google Scholar 

  100. Weinstein, D. C., et al. (1994). The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. Cell, 78(4), 575–588.

    CAS  PubMed  Google Scholar 

  101. Kubo, A., et al. (2004). Development of definitive endoderm from embryonic stem cells in culture. Development, 131(7), 1651–1662.

    CAS  PubMed  Google Scholar 

  102. Wong, A. P., et al. (2012). Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nature Biotechnology, 30(9), 876–882.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Mou, H., et al. (2012). Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell Stem Cell, 10(4), 385–397.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Besnard, V., et al. (2004). Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues. Gene Expression Patterns, 5(2), 193–208.

    CAS  PubMed  Google Scholar 

  105. Uetzmann, L., Burtscher, I., & Lickert, H. (2008). A mouse line expressing Foxa2-driven Cre recombinase in node, notochord, floorplate, and endoderm. Genesis, 46(10), 515–522.

    CAS  PubMed  Google Scholar 

  106. Stahlman, M. T., Gray, M. E., & Whitsett, J. A. (1998). Temporal-spatial distribution of hepatocyte nuclear factor-3beta in developing human lung and other foregut derivatives. Journal of Histochemistry and Cytochemistry, 46(8), 955–962.

    CAS  PubMed  Google Scholar 

  107. Zhou, L., et al. (1997). Hepatocyte nuclear factor-3beta limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo. Developmental Dynamics, 210(3), 305–314.

    CAS  PubMed  Google Scholar 

  108. Wan, H., et al. (2004). Foxa2 is required for transition to air breathing at birth. Proceedings of the National Academy of Sciences of the United States of America, 101(40), 14449–14454.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Wan, H., et al. (2004). Foxa2 regulates alveolarization and goblet cell hyperplasia. Development, 131(4), 953–964.

    CAS  PubMed  Google Scholar 

  110. Hao, Y., et al. (2013). Pyocyanin-induced mucin production is associated with redox modification of FOXA2. Respiratory Research, 14(1), 82.

    PubMed  PubMed Central  Google Scholar 

  111. Paranjapye, A., et al. (2020). The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells. American Journal of Physiology. Lung Cellular and Molecular Physiology, 319(1), L126-l136.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Serra, M., et al. (2017). Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification. Development, 144(21), 3879–3893.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Chen, Y. W., et al. (2017). A three-dimensional model of human lung development and disease from pluripotent stem cells. Nature Cell Biology, 19(5), 542–549.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Park, K. S., et al. (2006). Transdifferentiation of ciliated cells during repair of the respiratory epithelium. American Journal of Respiratory Cell and Molecular Biology, 34(2), 151–157.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The author, Yijian Lin, would like to thank all facilities managers, especially Meihua WU in the Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Chain.

Funding

This work was supported by grants from The General Program (Key program, Major Research Plan) of National Natural Science Foundation of China (82070021), Research Project of Jinan Microecological Biomedicine Shandong Laboratory (JNL-2022020B), Quanzhou City Science & Technology Program of China: Quanzhou High-level talents Project (2020C001R) and Quanzhou High-level talent team project (2020CT001).

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Authors and Affiliations

  1. Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

    Yijian Lin, Dachun Wang & Yiming Zeng

  2. Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China

    Yijian Lin & Yiming Zeng

  3. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

    Yijian Lin & Yiming Zeng

  4. Respiratory Medicine Center of Fujian Province, Quanzhou, 362000, Fujian Province, People’s Republic of China

    Yijian Lin & Yiming Zeng

  5. The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Medical School at Houston, Houston, TX, USA

    Dachun Wang

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  1. Yijian Lin
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Yijian Lin: Conceptualization, Writing (original draft, review, and editing).

Dachun Wang: Writing (review, and editing), Supervision.

Yiming Zeng: Writing (review, and editing), Supervision.

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Correspondence to Dachun Wang or Yiming Zeng.

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Lin, Y., Wang, D. & Zeng, Y. A Maverick Review of Common Stem/Progenitor Markers in Lung Development. Stem Cell Rev and Rep 18, 2629–2645 (2022). https://doi.org/10.1007/s12015-022-10422-z

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  • DOI: https://doi.org/10.1007/s12015-022-10422-z

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