Skip to main content
SpringerLink
Log in
Book cover

Stem Cells Handbook pp 455–472Cite as

Stem Cells in Lung Morphogenesis, Regeneration, and Carcinogenesis

  • Chapter

  • 368 Accesses

Abstract

Two levels of epithelial progenitors are involved in lung morphogenesis: multipotent undifferentiated cells (lung primordial cells) and pluripotent regiospecific (bronchial, bronchiolar, and alveolar) stem cells. The trachea and bronchi are lined by pseudostratified columnar epithelium (ciliated, mucous and basal cells). The bronchioles are lined by simple columnar epithelium (ciliated and Clara cells). Pulmonary neuroendocrine cells (PNECs) are also present. The alveolar ducts and sacs and the alveolar zone of the respiratory bronchioles are lined by cuboid alveolar type II cells and squamous alveolar type I cells. These regions all originate from evagination of ventral foregut endoderm containing lung primordial cells, into the surrounding visceral mesoderm with budding and branching, with their specific determination established as early as the pseudoglandular period of lung development. Tracheobronchial glands arise from specialized outpockets of basally situated surface cells. Bronchial stem cells are identified as label-retaining cells after pulsing with 3H thymidine or BrdU and can be found after injury in tracheal gland ducts as well as systematically distributed along the surface of the trachea and bronchi. In vitro and in vivo studies suggest that basal cells and columnar cells retain plasticity to regenerate a complete mucociliary epithelium. Clara cells represent the principal progenitor pool of the bronchiolar epithelium and are an example of a transit-amplifying cell population. True stem cells may proliferate after injury and depletion of the Clara cell population and are located in association with PNECs and also at the junction between the bronchioli and alveolar ducts. The stem cell for the alveolar epithelium is the early embryonic type II cell, which can give rise to progeny that differentiate to type I or type II cells. The preferential distribution of type II cell clusters in the adult lung supports the existence of type II stem cell niches. According to the current theory, the regiospecific stem cells are the most relevant targets for transformation and thus the source of lung cancer. The mixed phenotype of many lung carcinomas and studies of bronchial carcinogenesis suggest origin from a common un- or retrodifferentiated stem cell. Prospective treatments for common lung diseases, transplantation, gene transfer, and tumor therapy would all be advanced by a greater understanding of lung stem cells.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   199.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   259.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adamson, L. Y. R. and Bowden, D. H. (1974) The type 2 cell as progenitor of alveolar epithelial regeneration: a cytodynamic study in mice after exposure to oxygen. Lab. Invest. 30:35–42.

    PubMed  CAS  Google Scholar 

  • Adamson, L. Y. R. and Bowden, D. H. (1975) Derivation of type 1 epithelium from type 2 cells in the developing rat lung. Lab. Invest. 32: 736–745.

    PubMed  CAS  Google Scholar 

  • Alcorn, J. L., Smith, M. E., Smith, J. F., Margraf, L. R., and Mendelsohn, C. R. (1997) Primary cell culture of human type II pneumonocytes: maintenance of a differentiated phenotype and transfection with recombinant adenoviruses. Am. J. Respir. Cell Mol. Biol. 17:672–682.

    Article  PubMed  CAS  Google Scholar 

  • Balfour, F. M. (1881) A treatise on comparative embryology: the alimentary canal and its appendages. In: The Chordata, vol. 2, MacMillan, London, UK, pp. 628–630.

    Google Scholar 

  • Basbaum, C. and Jany, B. (1990) Plasticity in the airway epithelium. Am. J. Physiol. 259:L38—L46.

    Google Scholar 

  • Batenburg, J. J. (1992) Surfactant phospholipids: synthesis and storage. Am. J. Physiol. (Lung Cell. Mol. Physiol. 6) 262:L367—L385.

    Google Scholar 

  • Batenburg, J. J., Otto-Verberne, C. J. M., ten Have-Opbroek, A. A. W., and Klazinga, W. (1988) Isolation of alveolar type II cells from fetal rat lung by differential adherence in monolayer culture. Biochim. Biophys. Acta 960:441–453.

    Article  PubMed  CAS  Google Scholar 

  • Belinsky, S. A., Lechner, J. F., and Johnson, N.F. (1995) An improved method for the isolation of type II and Clara cells from mice. In Vitro Cell. Dev. Biol. Anim. 31:361–366.

    Article  PubMed  CAS  Google Scholar 

  • Benali, R., Tournier, J. M., Chevillard, M., et al. (1993) Tubule formation by human surface respiratory epithelial cells cultured in a threedimensional collagen lattice. Am. J. Physiol. 264:L183—L192.

    Google Scholar 

  • Bernacki, S. H., Nelson, A. L., Abdullah, L., et al. (1999) Mucin gene expression during differentiation of human airway epithelia in vitro: muc4 and muc5b are strongly induced. Am. J. Respir. Cell Mol. Biol. 20:595–604.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., Brazelton, T. R., and Weimann, J. M. (2001) The evolving concept of a stem cell: entity or function? Cell 105:829–841.

    Article  PubMed  CAS  Google Scholar 

  • Blenkinsopp, W. K. (1967) Proliferation of respiratory tract epithelium in the rat. Exp.Cell Res. 46:144–154.

    Article  PubMed  CAS  Google Scholar 

  • Boers, J. E., Ambergen, A. W., and Thunnissen, F. B. (1998) Number and proliferation of basal and parabasal cells in normal human airway epithelium. Am. J. Respir. Crit. Care Med. 157:2000–2006.

    Article  PubMed  CAS  Google Scholar 

  • Boers, J. E., den Brok, J. L., Koudstaal, J., Arends, J. W., and Thunnissen, F. B. (1996) Number and proliferation of neuroendocrine cells in normal human airway epithelium. Am. J. Respir. Crit. Care Med. 154: 758–763.

    Article  PubMed  CAS  Google Scholar 

  • Boers, J. E., Ambergen, A. W., and Thunnissen, F. B. (1999) Number and proliferation of clara cells in normal human airway epithelium. Am. J. Respir. Crit. Care Med. 159(5 Pt. 1):1585–1591.

    Article  PubMed  CAS  Google Scholar 

  • Borges, M., Linnoila, R. I., Van de Velde, H. J., et al. (1997) An achaetescute homologue essential for neuroendocrine differentiation in the lung. Nature 386:852–855.

    Article  PubMed  CAS  Google Scholar 

  • Borthwick, D. W., West, J. D., Keighren, M. A., Flockhart, J. H., Innes, B. A., and Dorin, J. R. (1999) Murine submucosal glands are clonally derived and show a cystic fibrosis gene-dependent distribution pattern. Am. J. Respir. Cell Mol. Biol. 20:1181–1189.

    Article  PubMed  CAS  Google Scholar 

  • Borthwick, D. W., Shahbazian, M., Todd, K. Q., Dorin, J. R., and Randell, S. H. (2001) Evidence for stem-cell niches in the tracheal epithelium. Am. J. Respir. Cell Mol. Biol. 24:662–670.

    Article  PubMed  CAS  Google Scholar 

  • Boyden, E. A. (1972) Development of the human lung. In: Brennemann’s Practise of Pediatrics, vol. 4, Harper & Row, Hagerstown, MD, pp. 1–12.

    Google Scholar 

  • Bragg, A. D., Moses, H. L., and Serra, R. (2001) Signaling to the epithelium is not sufficient to mediate all of the effects of transforming growth factor 13 and bone morphogenetic protein 4 on murine embryonic lung development. Mech. Dey. 109:13–26.

    Article  CAS  Google Scholar 

  • Brandsma, A. E., ten Have-Opbroek, A. A. W., Vulto, I. M., Molenaar, J. C., and Tibboel, D. (1994a) Alveolar epithelial composition and architecture of the late fetal pulmonary acinus: an immunocytochemical and morphometric study in a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. Exp. Lung Res. 20:491–515.

    Article  PubMed  CAS  Google Scholar 

  • Brandsma, A. E., Tibboel, D., Vulto, I. M., De Vijlder, J. J. M., ten HaveOpbroek, A. A. W., and Wiersinga, W. M. (1994b) Inhibition of T3receptor binding by nitrofen. Biochim. Biophys. Acta 1201:266–270.

    Article  PubMed  CAS  Google Scholar 

  • Breuer, R., Zajicek, G., Christensen, T. G., Lucey, E. C., and Snider, G. L. (1990) Cell kinetics of normal adult hamster bronchial epithelium in the steady state. Am. J. Respir. Cell Mol. Biol. 2:51–58.

    Article  PubMed  CAS  Google Scholar 

  • Bucher, U. and Reid, L. (1961) Development of the mucus secreting elements in human lung. Thorax 16:219–225.

    Article  PubMed  CAS  Google Scholar 

  • Buckpitt, A., Buonarati, M., Avey, L. B., Chang, A. M., Morin, D., and Plopper, C. G. (1992) Relationship of cytochrome P450 activity to Clara cell cytotoxicity. II. Comparison of stereoselectivity of naphthalene epoxidation in lung and nasal mucosa of mouse, hamster, rat and rhesus monkey. J. Pharmacol. Exp. Ther. 261(1):364–372.

    PubMed  CAS  Google Scholar 

  • Cardoso, W. V. (2001) Molecular regulation of lung development. Annu. Rev. Physiol. 63:471–494.

    Article  PubMed  CAS  Google Scholar 

  • Cardoso, W. V. and Williams, M. C. (2001) Basic mechanisms of lung development: Eighth Woods Hole Conference on lung cell biology 2000. Am. J. Respir. Cell Mol. Biol. 25 (2):137–140.

    Article  PubMed  CAS  Google Scholar 

  • Chinoy, M., Zgleszewski, S. E., Cilley, R. E., and Krummel, T.M. (2000) Dexamethasone enhances ras-recision gene expression in cultured murine fetal lungs: role in development. Am. J. Physiol. Lung Cell. Mol. Physiol. 279:L312–L318.

    Google Scholar 

  • Cilley, R. E., Zgleszewski, S. E., Krummel, T. M., and Chinoy, M. R. (1997) Nitrofen dose dependent gestational day-specific murine lung hypoplasia and left-sided diaphragmatic hernia. Am. J. Physiol. Lung Cell. Mol. Physiol. 272:L362–L371.

    Google Scholar 

  • Clara, M. (1937) Zur Histobiologie des Bronchalepithels. Z. Mikrosk. Anat. Forsch. 41:321–347.

    Google Scholar 

  • Corti, M., Brody, A. R., and Harrison, J. H. (1996) Isolation and primary culture of murine alveolar type II cells. Am. J. Respir. Cell Mol. Biol. 14(4):309–315.

    Article  PubMed  CAS  Google Scholar 

  • Cutz, E., Yeger, H., Wong, V., Bienkowski, E., and Chan, W. (1985) In vitro characteristics of pulmonary neuroendocrine cells isolated from rabbit fetal lung. I. Effects of culture media and nerve growth factor. Lab. Invest. 53(6):672–683.

    PubMed  CAS  Google Scholar 

  • DeMayo, F. J., Finegold, M. J., Hansen, T. N., Stanley, L. A., Smith, B., and Bullock, D. W. (1991) Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice. Am. J. Physiol. 261(2 Pt. 1):L70–L76.

    Google Scholar 

  • Donnelly, G. M., Haack, D. G., and Heird, C. S. (1982) Tracheal epithelium: cell kinetics and differentiation in normal rat tissue. Cell Tissue Kinet. 15:119–130.

    PubMed  CAS  Google Scholar 

  • Duan, D., Yue, Y., Zhou, W., et al. (1999) Submucosal gland development in the airway is controlled by lymphoid enhancer binding factor 1 (LEF1). Development 126:4441–4453.

    PubMed  CAS  Google Scholar 

  • Dubreuil, G., Lacoste, A., and Raymond, R. (1936) Observations sur le développement du poumon humain. Bull. Histol. Appliq. Physiol. Pathol. 13:235–245.

    Google Scholar 

  • Ebe, T. (1969) Light and electron microscope studies on experimental pneumonitis induced by blasticidin-S, with special reference to alveolar regeneration. Arch. Histol. Jpn 30:149–182.

    Article  PubMed  CAS  Google Scholar 

  • Engelhardt, J. F. (2001) Stem cell niches in the mouse airway. Am. J. Respir. Cell Mol. Biol. 24(6):649–652.

    Article  PubMed  CAS  Google Scholar 

  • Engelhardt, J. F., Schlossberg, H., Yankaskas, J. R., and Dudus, L. (1995) Progenitor cells of the adult human airway involved in submucosal gland development. Development 121:2031–2046.

    PubMed  CAS  Google Scholar 

  • Erjefalt, J. S. and Persson, C. G. A. (1997) Airway epithelial repair: breathtakingly quick and multipotentially pathogenic. Thorax 52:1010–1012.

    Article  PubMed  CAS  Google Scholar 

  • Evans, M. J., Cabral, L. J., Stephens, R. J., and Freeman, G. (1975) Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2. Exp. Mol. Pathol. 22:142–150.

    Article  PubMed  CAS  Google Scholar 

  • Evans, M. J., Johnson, L. V., Stephens, R. J., and Freeman, G. (1976) Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab. Invest. 35(3):246–257.

    PubMed  CAS  Google Scholar 

  • Evans, M. J., Cabral-Anderson, L. J., and Freeman, G. (1978) Role of the Clara cell in renewal of the bronchiolar epithelium. Lab. Invest. 38(6): 648–653.

    PubMed  CAS  Google Scholar 

  • Ford, J. R. and Terzaghi-Howe, M. (1992) Characteristics of magnetically separated rat tracheal epithelial cell populations. Am. J. Physiol. 263:L568–L574.

    Google Scholar 

  • Gazdar, A. F. and Minna, J. D. (1996) NCI series of cell lines: an historical perspective. J. Cell. Biochem. Suppl. 24:1–11.

    Article  PubMed  CAS  Google Scholar 

  • Giangreco, A. S., Reynolds, D., and Stripp, B. R. (2002) Terminal bronchioles harbor a unique airway stem cell population that localizes to the broncho-alveolar duct junction. Am. J. Pathol. 161:173–182.

    Article  PubMed  Google Scholar 

  • Goerke, J. (1974) Lung surfactant. Biochim. Biophys. Acta 344:241–261.

    Article  PubMed  CAS  Google Scholar 

  • Gruenert, D. C., Basbaum, C. B., Welsh, M. J., Li, M., Finkbeiner, W. E., and Nadel, J. A. (1988) Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. Proc. Natl. Acad. Sci. USA 85:5951–5955.

    Article  PubMed  CAS  Google Scholar 

  • Gruenert, D. C., Finkbeiner, W. E., and Widdicombe, J. H. (1995) Culture and transformation of human airway epithelial cells. Am. J. Physiol. 268:L347–L360.

    Google Scholar 

  • Hackett, B. P. and Gitlin, J.D. (1992) Cell-specific expression of a Clara cell secretory protein-human growth hormone gene in the bronchiolar epithelium of transgenic mice. Proc. Natl. Acad. Sci. USA 89(19): 9079–9083.

    Article  PubMed  CAS  Google Scholar 

  • Haugen, A. and Aune, T. (1986) Culture of rabbit pulmonary Clara cells. Proc. Soc. Exp. Biol. Med. 182(2):277–281.

    PubMed  CAS  Google Scholar 

  • Heckman, C. A., Marchok, A. C., and Nettesheim, P. (1978) Respiratory tract epithelium in primary culture: concurrent growth and differentiation during establishment. J. Cell Sci. 32:269–291.

    PubMed  CAS  Google Scholar 

  • Hislop, A. and Reid, L. (1974) Development of the acinus in the human lung. Thorax 29:90–94.

    Article  PubMed  CAS  Google Scholar 

  • Ho, Y. S. (1994) Transgenic models for the study of lung biology and disease. Am. J. Physiol. 266(4 Pt. 1):L319–L353.

    Google Scholar 

  • Hogan, B. L., Grindley, J., Bellusci, S., Dunn, N. R., Emoto, H., and Itoh, N. (1997) Branching morphogenesis of the lung: new models for a classical problem. Cold Spring Harbor Symp. Quant. Biol. 62:249–256.

    Article  PubMed  CAS  Google Scholar 

  • Hong, K. U., Reynolds, S. D., Giangreco A., Hurley, C. M., and Stripp, B. R. (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(6):671–681.

    Article  PubMed  CAS  Google Scholar 

  • Hook, G. E., Brody, A. R., Cameron, G. S., Jetten, A. M., Gilmore, L. B., and Nettesheim, P. (1987) Repopulation of denuded tracheas by Clara cells isolated from the lungs of rabbits. Exp. Lung Res. 12:311–329.

    Article  PubMed  CAS  Google Scholar 

  • Hundertmark, S., Ragosch, V., Zimmermann, B., Halis, G., Arabin, B., and Weitzel, H. K. (1999) Effect of dexamethasone, triiodothyronine, and dimethyl-isopropylthyronine on lung maturation of the fetal rat lung. J. Perinat. Med. 27:309–315.

    Article  PubMed  CAS  Google Scholar 

  • Inayama, Y., Hook, G. E. R., Brody, A. R. et al. (1988) The differentiation potential of tracheal basal cells. Lab. Invest. 58:706–717.

    PubMed  CAS  Google Scholar 

  • Inayama, Y., Hook, G. E. R., Brody, A. R., et al. (1989) In vitro and in vivo growth and differentiation of clones of tracheal basal cells. Am. J. Pathol. 134:539–549.

    PubMed  CAS  Google Scholar 

  • Jeffery, P. K., Gaillard, D., and Moret, S. (1992) Human airway secretory cells during development and in mature airway epithelium. Eur. Respir. J. 5:93–104.

    PubMed  CAS  Google Scholar 

  • Johnson, N. F. and Hubbs, A. F. (1990) Epithelial progenitor cells in the rat trachea. Am. J. Respir. Cell Mol. Biol. 3:579–585.

    Article  PubMed  CAS  Google Scholar 

  • Jorissen, M., Van der Schueren, B., van den Berghe, H., and Cassiman, J. J. (1989) The preservation and regeneration of cilia on human nasal epithelial cells cultured in vitro. Arch. Otorhinolaryngol. 246:308–314.

    Article  CAS  Google Scholar 

  • Kauffman, S. L., Burri, P. H., and Weibel, E. R. (1974) The postnatal growth of the rat lung. II. Autoradiography. Anat. Rec. 180:63–76.

    Article  PubMed  CAS  Google Scholar 

  • Keijzer, R., Van Tuyl, M., Meijers, C., et al. (2001) The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development. Development 128:503–511.

    PubMed  CAS  Google Scholar 

  • Khoor, A., Gray, M. E., Singh, G., and Stahlman, M. T. (1996) Ontogeny of Clara cell-specific protein and its mRNA: their association with neuroepithelial bodies in human fetal lung and in bronchopulmonary dysplasia. J. Histochem. Cytochem. 44(12):1429–1438.

    Article  PubMed  CAS  Google Scholar 

  • Koo, J. S., Yoon, J. H., Gray, T., Norford, D., Jetten, A. M., and Nettesheim, P. (1999) Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: changes in mucin gene expression. Am. J. Respir. Cell Mol. Biol. 20: 43–52.

    Article  PubMed  CAS  Google Scholar 

  • Krause, D. S., Theise, N. D., Collector, M. I., Henegariu, O., Hwang, S., Gardner, R., Neutzel, S., and Sharkis, S. J. (2001) Multi-organ, multilineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377.

    Article  PubMed  CAS  Google Scholar 

  • Lawson, G. W., Van Winkle, L. S., Toskala, E., Senior, R. M., Parks, W. C., and Plopper, C. G. (2002) Mouse strain modulates the role of the ciliated cell in acute tracheobronchial airway injury-distal airways. Am. J. Pathol. 160:315–327.

    Article  PubMed  Google Scholar 

  • Lebeche, D., Malpel, S., and Cardoso, W. V. (1999) Fibroblast growth factor interactions in the developing lung. Mech. Dev. 86(1–2):125–136.

    Article  PubMed  CAS  Google Scholar 

  • Lechner, J. F., Haugen, A., Autrup, H., McClendon, I. A., Trump, B. F., and Harris, C. C. (1981) Clonal growth of epithelial cells from normal adult human bronchus. Cancer Res. 41(6):2294–2304.

    PubMed  CAS  Google Scholar 

  • Lechner, J. F., Fugaro, J. M., Wong, Y., Pass, H. I., Harris, C. C., and Belinsky, S. A. (2001) Perspective: cell differentiation theory may advance early detection of and therapy for lung cancer. Radiat. Res. 155:235–238.

    Article  PubMed  CAS  Google Scholar 

  • Linnoila, R.I., Mulshine, J.L., Steinberg, S.M., and Gazdar, A.F. (1992) Expression of surfactant-associated protein in non-small cell lung cancer: a discriminant between biologic subsets. J. Natl. Cancer Inst. Monogr. 13:61–66.

    PubMed  Google Scholar 

  • Linnoila, R. I., Gazdar, A. F., Funa, K., and Becker, K. L. (1993) Longterm selective culture of hamster pulmonary endocrine cells. Anat. Rec. 236(1):231–240.

    Article  PubMed  CAS  Google Scholar 

  • Linnoila, R. I., Sahu, A., Miki, M., Ball, D. W., and DeMayo, F. J. (2000a) Morphometric analysis of CC10-hASH1 transgenic mouse lung: a model for bronchiolization of alveoli and neuroendocrine carcinoma. Exp. Lung Res. 26:595–615.

    Article  PubMed  CAS  Google Scholar 

  • Linnoila, R. I., Szabo, E., Demayo, F., Witschi, H., Sabourin, C., and Malkinson, A. (2000b) The role of CC10 in pulmonary carcinogenesis: from a marker to tumor suppression. Ann. NY Acad. Sci. 923: 249–267.

    Article  PubMed  CAS  Google Scholar 

  • Liu, J. Y., Nettesheim, P., and Randell, S. H. (1994) Growth and differentiation of tracheal epithelial progenitor cells. Am. J. Physiol. 266: L296–L307.

    Google Scholar 

  • Loosli, C. G. and Potter, E. L. (1959) Pre- and postnatal development of the respiratory portion of the human lung. Am. Rev. Respir. Dis. 80: 5–23.

    PubMed  CAS  Google Scholar 

  • Lum, H., Schwartz, L. W., Dungworth, D. L., and Tyler, W. S. (1978) A comparative study of cell renewal after exposure to ozone or oxygen: Response of terminal bronchiolar epithelium in the rat. Am. Rev. Respir. Dis. 118(2):335–345.

    PubMed  CAS  Google Scholar 

  • Masui, T., Lechner, J. F., Yoakum, G. H., Willey, J. C., and Harris, C. C. (1986a) Growth and differentiation of normal and transformed human bronchial epithelial cells. J. Cell Physiol. Suppl. 4:73–81.

    Article  PubMed  CAS  Google Scholar 

  • Masui, T., Wakefield, L. M., Lechner, J. F., LaVeck, M. A., Sporn, M. B., and Harris, C. C. (1986b) Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc. Natl. Acad. Sci. USA 83:2438–2442.

    Article  PubMed  CAS  Google Scholar 

  • McDowell, E. M. (1987) Bronchogenic carcinomas. In: Lung Carcinomas, Part IV, Neoplasms of the Human Lung (McDowell, E. M., ed.), Churchill Livingstone, Edinburgh, pp. 255–285.

    Google Scholar 

  • McDowell, E. M., Newkirk, C., and Coleman, B. (1985) Development of hamster tracheal epithelium: II. Cell proliferation in the fetus. Anat. Rec. 213:448–456.

    Article  PubMed  CAS  Google Scholar 

  • Mercer, R. R., Russell, M. L., Roggli, V. L., and Crapo, J. D. (1994) Cell number and distribution in human and rat airways. Am. J. Respir. Cell Mol. Biol. 10:613–624.

    Article  PubMed  CAS  Google Scholar 

  • Nasiell, M., Auer, G., and Kato, H. (1987) Cytologic studies in man and animals on development of bronchogenic carcinoma. In: Lung Carcinomas, Part III, Progression to Neoplasia (McDowell, E. M., ed.), Churchill Livingstone, Edinburgh, pp. 207–242.

    Google Scholar 

  • Nord, M., Lag, M., Cassel, T. N., et al. (1998) Regulation of CCSP (PCBBP/uteroglobin) expression in primary cultures of lung cells: involvement of C/EBP. DNA Cell Biol. 17(5):481–492.

    Article  PubMed  CAS  Google Scholar 

  • Oie, H. K., Russell, E. K., Carney, D. N., and Gazdar, A. F. (1996) Cell culture methods for the establishment of the NCI series of lung cancer cell lines. J. Cell. Biochem. Suppl. 24:24–31.

    Article  PubMed  CAS  Google Scholar 

  • Oomen, L. C. J. M., ten Have-Opbroek, A. A. W., Hageman, P. C., et al. (1990) Fetal mouse alveolar type II cells in culture express several type II cell characteristics found in vivo, together with Major Histocompatibility antigens. Am. J. Respir. Cell Mol. Biol. 3:325–339.

    Article  PubMed  CAS  Google Scholar 

  • Oomen, L. C. J. M., Calafat, J., ten Have-Opbroek, A. A. W., Egberts, J., and Demant, P. (1992) Derivation of tumorigenic and non-tumorigenic mouse alveolar type II cell lines from fetal type II cells after a combined in vivo/in vitro carcinogen treatment. Int. J. Cancer 52: 290–297.

    Article  PubMed  CAS  Google Scholar 

  • Otto-Verberne, C. J. M. and Ten Have-Opbroek, A. A. W. (1987) Development of the pulmonary acinus in fetal rat lung: a study based on an antiserum recognizing surfactant-associated proteins. Anat. Embryol. 175:365–373.

    Article  PubMed  CAS  Google Scholar 

  • Otto-Verberne, C. J. M., ten Have-Opbroek, A. A. W., Balkema, J. J., and Franken, C. (1988) Detection of the type II cell or its precursor before week 20 of human gestation, using antibodies against surfactant-associated proteins. Anat. Embryol. 178:29–39.

    Article  PubMed  CAS  Google Scholar 

  • Otto-Verberne, C. J. M., ten Have-Opbroek, A. A. W., and De Vries, E. C. P. (1990) Expression of the major surfactant-associated protein, SP-A, in type II cells of human lung before 20 weeks of gestation. Eur. J. Cell Biol. 53:13–19.

    PubMed  CAS  Google Scholar 

  • Perl, A. K. T. and Whitsett, J. A. (1999) Molecular mechanisms controlling lung morphogenesis. Clin. Genet. 56:14–27.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G. and ten Have-Opbroek, A. A. W. (1994) Anatomical and histological classification of the bronchioles. In: Diseases of the Bronchioles (Epler, G. R., ed.), Raven, New York, pp. 15–25.

    Google Scholar 

  • Plopper, C. G., Hill, L. H., and Mariassy, A. T. (1980) Ultrastructure of the nonciliated bronchiolar epithelial (Clara) cell of mammalian lung. III. A study of man with comparison of 15 mammalian species. Exp. Lung Res. 1(2):171–180.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G., Mariassy, A. T., Wilson, D. W., Alley, J. L., Nishio, S. J., and Nettesheim, P. (1983) Comparison of nonciliated tracheal epithelial cells in six mammalian species: ultrastructure and population densities. Exp. Lung Res. 5(4):281–294.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G., Alley, J. L., and Weir, A.J. (1986) Differentiation of tracheal epithelium during fetal lung maturation in the Rhesus monkey Macaca mulatta. Am. J. Anat. 175:59–71.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G., Heidsiek, J. G., Weir, A. J., St. George, J. A., and Hyde, D. M. (1989) Tracheobronchial epithelium in the adult Rhesus monkey: a quantitative histochemical and ultrastructural study. Am. J. Anat. 184:31–40.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G., Chang, A. M., Pang, A., and Buckpitt, A.R. (1991) Use of microdissected airways to define metabolism and cytotoxicity in murine bronchiolar epithelium. Exp. Lung Res. 17(2):197–212.

    Article  PubMed  CAS  Google Scholar 

  • Plopper, C. G., Macklin, J., Nishio, S. J., Hyde, D. M., and Buckpitt, A. R. (1992) Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of naphthalene. Lab. Invest. 67(5):553–565.

    PubMed  CAS  Google Scholar 

  • Randell, S. H., Comment, C. E., Ramaekers, F. C. S., and Nettesheim, P. (1991) Properties of rat tracheal epithelial cells separated based on expression of cell surface β-galactosyl end groups. Am. J. Respir. Cell Mol. Biol. 4:544–554.

    Article  PubMed  CAS  Google Scholar 

  • Ray, M. K., Magdaleno, S. W., Finegold, M. J., and DeMayo, F. J. (1995) Cis-acting elements involved in the regulation of mouse Clara cell-specific 10-kDa protein gene: in vitro and in vivo analysis. J. Biol. Chem. 270(6):2689–2694.

    Article  PubMed  CAS  Google Scholar 

  • Rehm, S., Ward, J. M., ten Have-Opbroek, A. A. W., et al. (1988) Mouse papillary lung tumors transplacentally induced by N-nitrosoethylurea: evidence for alveolar type II cell origin by comparative light microscopic, ultrastructural, and immunohistochemical studies. Cancer Res. 48:148–160.

    PubMed  CAS  Google Scholar 

  • Rehm, S., Takahashi, M., Ward, J. M., Singh, G., Katyal, S. L., and Henneman, J. R. (1989) Immunohistochemical demonstration of Clara cell antigen in lung tumors of bronchiolar origin induced by N-nitrosodiethylamine in Syrian golden hamsters. Am. J. Pathol. 134:79–87.

    PubMed  CAS  Google Scholar 

  • Rehm, S., Lijinski, W., Singh, G., and Katyal, S. L. (1991) Mouse bronchiolar cell carcinogenesis. Am. J. Pathol. 139:413–422.

    PubMed  CAS  Google Scholar 

  • Reynolds, S. D., Hong, K. U., Giangreco, A., et al. (2000a) Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 278(6):L1256–L1263.

    Google Scholar 

  • Reynolds, S. D., Giangreco, A., Power, J. H., and Stripp, B. R. (2000b) Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am. J. Pathol. 156(1):269–278.

    Article  PubMed  CAS  Google Scholar 

  • Sandmoller, A., Halter, R., Gomez-La-Hoz, E., et al. (1994) The uteroglobin promoter targets expression of the SV40 T antigen to a variety of secretory epithelial cells in transgenic mice. Oncogene 9(10):2805–2815.

    PubMed  CAS  Google Scholar 

  • Schüller, H. M. (1987) Experimental carcinogenesis in the peripheral lung. In: Lung Carcinomas, Part III, Progression to Neoplasia (McDowell, E. M., ed.), Churchill Livingstone, Edinburgh, pp. 243–254.

    Google Scholar 

  • Schwarz, M. A., Zhang, F., Lane, J. E., et al. (2000) Angiogenesis and morphogenesis of murine fetal distal lung in an allograft model. Am. J. Physiol. Lung Cell. Mol. Physiol. 278:L1000–L1007.

    Google Scholar 

  • Sell, S. and Pierce, G. B. (1994) Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab. Invest. 70:6–22.

    PubMed  CAS  Google Scholar 

  • Shannon, J. M. (1994) Induction of alveolar type II cell differentiation in fetal tracheal epithelium by grafted distal lung mesenchyme. Dev. Biol. 166(2):600–614.

    Article  PubMed  CAS  Google Scholar 

  • Shannon, J. M., Nielsen, L. D., Gebb, S. A., and Randell, S. H. (1998) Mesenchyme specifies epithelial differentiation in reciprocal recombinants of embryonic lung and trachea. Dev. Dyn. 212(4):482–494.

    Article  PubMed  CAS  Google Scholar 

  • Singh, G. and Katyal, S. L. (1984) An immunologic study of the secretory products of rat Clara cells. J. Histochem. Cytochem. 32:49–54.

    Article  PubMed  CAS  Google Scholar 

  • Sorokin, S. P. (1966) A morphologic and cytochemical study on the great alveolar cell. J. Histochem. Cytochem. 14:884–897.

    Article  PubMed  CAS  Google Scholar 

  • Sorokin, S. P., Hoyt, R. F. Jr., and Grant, M. M. (1982) Development of neuroepithelial bodies in fetal rabbit lungs. I. Appearance and functional maturation as demonstrated by high-resolution light microscopy and formaldehyde-induced fluorescence. Exp. Lung Res. 3: 237–259.

    Article  PubMed  CAS  Google Scholar 

  • Speirs, V. and Cutz, E. (1993) An overview of culture and isolation methods suitable for in vitro studies on pulmonary neuroendocrine cells. Anat. Rec. 236(1):35–40.

    Article  PubMed  CAS  Google Scholar 

  • Speirs, V., Wang, Y. V., Yeger, H., and Cutz, E. (1992) Isolation and culture of neuroendocrine cells from fetal rabbit lung using immunomagnetic techniques. Am. J. Respir. Cell Mol. Biol. 6(1):63–67.

    Article  PubMed  CAS  Google Scholar 

  • Spooner, B. S. and Wessels, N. K. (1970) Mammalian lung development: interactions in primordium formation and bronchial morphogenesis. J. Exp. Zool. 175:445–454.

    Article  PubMed  CAS  Google Scholar 

  • Stahlman, M. T. and Gray, M. E. (1984) Ontogeny of neuroendocrine cells in human fetal lung. I. An electron microscopic study. Lab. Invest. 51(4):449–463.

    PubMed  CAS  Google Scholar 

  • Stearns, R. C., Paulauskis, J. D., and Godleski, J. J. (2001) Endocytosis of ultrafine particles by A549 cells. Am. J. Respir. Cell Mol. Biol. 24: 108–115.

    Article  PubMed  CAS  Google Scholar 

  • Stoner, G. D., Katoh, Y., Foidart, J. M., Myers, G. A., and Harris, C. C. (1980) Identification and culture of human bronchial epithelial cells. Meth. Cell Biol. 21A:15–35.

    Article  Google Scholar 

  • Stripp, B. R., Sawaya, P. L., Luse, D. S., et al. (1992) cis-acting elements that confer lung epithelial cell expression of the CC10 gene. J. Biol. Chem. 267(21):14,703–14,712.

    Google Scholar 

  • Stripp, B. R., Huffman, J. A., and Bohinski, R. J. (1994) Structure and regulation of the murine Clara cell secretory protein gene. Genomics 20(1):27–35.

    Article  PubMed  CAS  Google Scholar 

  • Stripp, B. R., Maxson, K., Mera, R., and Singh, G. (1995) Plasticity of airway cell proliferation and gene expression after acute naphthalene injury. Am. J. Physiol. 269(6 Pt. 1):L791–L799.

    Google Scholar 

  • Sunday, M., Willet, C. G., Graham, S. A., et al. (1995) Histochemical characterization of non-neuroendocrine tumors and neuroendocrine cell hyperplasia induced in hamster lung by 4-(methylnitrosamino)-1(3-pyridy1)-1-butanone with or without hyperoxia. Am. J. Pathol. 147: 740–752.

    PubMed  CAS  Google Scholar 

  • Tebar M., Destrée, O., De Vree, W. J. A., and ten Have-Opbroek, A. A. W. (2001a) Expression of Tcf/Lef and sFRP and localization of β catenin in the developing mouse lung. Mech. Dev. 109:437–440.

    Article  PubMed  CAS  Google Scholar 

  • Tebar, M., Boex, J. J. M., and ten Have-Opbroek, A. A. W. (2001b) Functional overexpression of wild-type p53 correlates with alveolar cell differentiation in the developing human lung. Anat. Rec. 263: 25–34.

    Article  PubMed  CAS  Google Scholar 

  • ten Have-Opbroek, A. A. W. (1975) Immunological study of lung development in the mouse embryo. I. Appearance of a lung-specific antigen, localized in the great alveolar cell. Dev. Biol. 46:390–403.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W. (1979) Immunological study of lung development in the mouse embryo. II. First appearance of the great alveolar cell, as shown by immunofluorescence microscopy. Dev. Biol. 69:408–423.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W. (1981) The development of the lung in mammals: an analysis of concepts and findings. Am. J. Anat. 162: 201–219.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W. (1986) The structural composition of the pulmonary acinus in the mouse: a scanning electron microscopical and developmental-biological analysis. Anat. Embryol. 174:49–57.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W. (1991) Lung development in the mouse embryo. Exp. Lung Res. 17:111–130.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W., and De Vries, E. C. P. (1993) Clara cell differentiation in the mouse: ultrastructural morphology and cytochemistry for surfactant protein A and Clara cell 10 kD protein. Microsc. Res. Technolol. 26:400–411.

    Article  Google Scholar 

  • ten Have-Opbroek, A. A. W. and Plopper, C. G. (1992) Morphogenetic and functional activity of type II cells in early fetal Rhesus monkey lungs: a comparison between primates and rodents. Anat. Rec. 234: 93–104.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W., Dubbeldam, J. A., and Otto-Verberne, C. J. M. (1988) Ultrastructural features of type II alveolar epithelial cells in early embryonic mouse lung. Anat. Rec. 221:846–853.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W., Hammond, W. G., and Benfield, J. R. (1990a) Bronchiolo-alveolar regions in adenocarcinoma arising from canine segmental bronchus. Cancer Leu. 55:177–182.

    Article  Google Scholar 

  • ten Have-Opbroek, A. A. W., Otto-Verberne, C. J. M., and Dubbeldam, J. A. (1990b) Ultrastructural characteristics of inclusion bodies of type II cells in late embryonic mouse lung. Anat. Embryol. 181:317–323.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W., Otto-Verberne, C. J. M., Dubbeldam, J. A., and Dijkman, J. H. (1991) The proximal border of the human respiratory unit, as shown by scanning and transmission electron microscopy and light microscopical cytochemistry. Anat. Rec. 229:339–354.

    Article  PubMed  Google Scholar 

  • ten Have-Opbroek, A. A. W., Hammond, W. G., Benfield, J. R., Teplitz, R. L., and Dijkman, J. H. (1993) Expression of alveolar type II cell markers in acinar adenocarcinomas and adenoid-cystic carcinomas arising from segmental bronchi: a study in a heterotopic bronchogenic carcinoma model in dogs. Am. J. Pathol. 142:1251–1264.

    Google Scholar 

  • ten Have-Opbroek, A.A.W., Benfield, JR., Hammond, W.G., Teplitz, R.L., and Dijkman, J.H. (1994) In favour of an oncofoetal concept of bronchogenic carcinoma development. Histol. Histopathol. 9:375–384.

    PubMed  Google Scholar 

  • ten Have-Opbroek, A.A.W., Benfield, JR., Hammond, W.G., and Dijkman, J.H. (1996) Alveolar stem cells in canine bronchial carcinogenesis. Cancer Lett. 101:211–217.

    Article  PubMed  CAS  Google Scholar 

  • ten Have-Opbroek, A.A.W., Benfield, JR., Van Krieken, J.H.J.H., and Dijkman, J.H. (1997) The alveolar type II cell is a pluripotential stem cell in the genesis of human adenocarcinomas and squamous cell carcinomas. Histol. Histopathol. 12:319–336.

    PubMed  Google Scholar 

  • ten Have-Opbroek, A.A.W., Shi, X.-B., and Gumerlock, P.H. (2000) 3-Methylcholanthrene triggers the differentiation of alveolar tumor cells from canine bronchial basal cells and an altered p53 gene promotes their clonal expansion. Carcinogenesis 21:1477–1484.

    Article  Google Scholar 

  • Terzaghi, M., Nettesheim, P., and Williams, M. L. (1978) Repopulation of denuded tracheal grafts with normal, preneoplastic, and neoplastic epithelial cell populations. Cancer Res. 38:4546–4553.

    PubMed  CAS  Google Scholar 

  • Tos, M. (1968) Development of the mucous glands in the human main bronchus. Anat. Anz. 123:376–389.

    PubMed  CAS  Google Scholar 

  • Tyler, N. K. and Plopper, C. G. (1985) Morphology of the distal conducting airways in Rhesus monkey lungs. Anat. Rec. 211:295–303.

    Article  PubMed  CAS  Google Scholar 

  • Van Lommel, A., Bolle, T., Fannes, W., and Lauweryns, J. M. (1999) The pulmonary neuroendocrine system: the past decade. Arch. Histol. Cytol. 62:1–16.

    Article  PubMed  Google Scholar 

  • Van Winkle, L. S., Buckpitt, A. R., Nishio, S. J., Isaac, J. M., and Plopper, C. G. (1995) Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice. Am. J.Physiol. 269(6 Pt. 1):L800—L818.

    Google Scholar 

  • Van Winkle, L. S., Buckpitt, A. R., and Plopper, C. G. (1996) Maintenance of differentiated murine Clara cells in microdissected airway cultures. Am. J. Respir. Cell Mol. Biol. 14(6):586–598.

    Article  PubMed  Google Scholar 

  • Walker, S. R., Hale, S., Malkinson, A. M., and Mason, R. J. (1989) Properties of isolated nonciliated bronchiolar cells from mouse lung. Exp. Lung Res. 15(4):553–573.

    Article  PubMed  CAS  Google Scholar 

  • Warburton, D., Schwarz, M., Tefft, D., Flores-Delgado, G., Anderson, K. D., and Cardoso, W. V. (2000) The molecular basis of lung morphogenesis. Mech. Dev. 92:55–81.

    Article  PubMed  CAS  Google Scholar 

  • Warburton, D., Tefft, D., Mailleux, A., et al. (2001) Do lung remodeling, repair, and regeneration recapitulate respiratory ontogeny? Am. J. Respir. Crit. Care Med. 164(10 Pt. 2):S59–S62.

    Article  Google Scholar 

  • Warburton, D., Wuenschell, C., Flores-Delgado, G., and Anderson, K. (2002) Commitment and differentiation of lung cell lineages. Biochem. Cell Biol. 76:971–995.

    Article  Google Scholar 

  • Weaver, M., Dunn, N. R., and Hogan, B. L. (2000) Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 127(12):2695–2704.

    PubMed  CAS  Google Scholar 

  • Weaver, T. E. (1991) Surfactant proteins and SP-D. Am. J. Respir. Cell Mol. Biol. 5:4–5.

    Article  PubMed  CAS  Google Scholar 

  • Wert, S. E., Glasser, S. W., Korfhagen, T. R., and Whitsett, J. A. (1993) Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice. Dev. Biol. 156(2):426–443.

    Article  PubMed  CAS  Google Scholar 

  • Whitcutt, M. J., Adler, K., and Wu, R. (1988) A biphasic chamber system for maintaining polarity of differentiation of cultured respiratory tract epithelial cells. In Vitro Cell. Dev. Biol. 24:420–428.

    Article  PubMed  CAS  Google Scholar 

  • Wuenschell, C. W., Sunday, M. E., Singh, G., Minoo, P., Slavkin, H. C., and Warburton, D. (1996) Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages. J. Histochem. Cytochem. 44(2):113–123.

    Article  PubMed  CAS  Google Scholar 

  • Yoakum, G. H., Lechner, J. F., Gabrielson, E. W., et al. (1985) Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene. Science 227:1174–1179.

    Article  PubMed  CAS  Google Scholar 

  • Zeng, X., Wert, S. E., Federici, R., Peters, K. G., and Whitsett, J. A. (1998) VEGF enhances pulmonary vasculogenesis and disrupts lung morphogenesis in vivo. Dev. Dyn. 211:215–227.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y. J., O’Neal, W. K., Randell, S. H., et al. (2002) Identification of dynein heavy chain 7 as an inner arm component of human cilia that is synthesized but not assembled in a case of primary ciliary dyskinesia. J. Biol. Chem. 277:17,906–17,915.

    Google Scholar 

  • Zimmermann, B. (1987) Lung organoid culture. Differentiation 36: 86–109.

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann, B. (1989) Secretion of lamellar bodies in type II pneumocytes in organoid culture: effects of colchicine and cytochalasin B. Exp. Lung Res. 15:31–47.

    Article  PubMed  CAS  Google Scholar 

  • Zoechbauer-Mueller, S., Gazdar, A. F., and Minna, J. D. (2002) Molecular pathogenesis of lung cancer. Annu. Rev. Physiol. 64: 681–708.

    Article  Google Scholar 

Download references

Authors
  1. Ank A. W. ten Have-Opbroek MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott H. Randell PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barry R. Stripp PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wadsworth Center and Ordway Research Institute, Empire State Plaza, Albany, NY, USA

    Stewart Sell MD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

ten Have-Opbroek, A.A.W., Randell, S.H., Stripp, B.R. (2004). Stem Cells in Lung Morphogenesis, Regeneration, and Carcinogenesis. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_41

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-411-5_41

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-367-1

  • Online ISBN: 978-1-59259-411-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation