Stem Cells Are Dispensable for Lung Homeostasis but Restore Airways After Injury

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 May 30

PMID 19478060

Citations 123

Authors

Adam Giangreco

Esther N Arwert

Ian R Rosewell

Joshua Snyder

Fiona M Watt

Barry R Stripp

Affiliations

Soon will be listed here.

Abstract

Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiolar stem cells to epithelial maintenance and repair. In normal and moderately injured airways chimeric patches were small in size and not associated with previously described stem cell niches. This finding suggested that single, randomly distributed progenitor cells maintain normal epithelial homeostasis. In contrast we found that repair following severe lung injury resulted in the generation of rare, large clonal cell patches that were associated with stem cell niches. This study provides evidence that epithelial stem cells are dispensable for normal airway homeostasis. We also demonstrate that stem cell activation and robust clonal cellular expansion occur only during repair from severe lung injury.

Citing Articles

DjsoxP-1 and Djsox5 are essential for tissue homeostasis and regeneration in Dugesia japonica.

Guo W, Liu X, Pang L, Kong Z, Lin Z, Ren J Cell Tissue Res. 2025; 399(3):337-350.

PMID: 39762587 DOI: 10.1007/s00441-024-03939-x.

Unlocking lung regeneration: insights into progenitor cell dynamics and metabolic control.

Yang J, Li Y, Huang Y, Chen H, Sui P Cell Regen. 2024; 13(1):31.

PMID: 39676102 PMC: 11646969. DOI: 10.1186/s13619-024-00212-y.

Short histological kaleidoscope - recent findings in histology. Part IV.

Sufletel R, Mihu C, Bosca A, Melincovici C, Marginean M, Jianu E Rom J Morphol Embryol. 2024; 65(3):377-393.

PMID: 39529332 PMC: 11657374. DOI: 10.47162/RJME.65.3.01.

Trained immunity inducers in cancer immunotherapy.

Sui Y, Berzofsky J Front Immunol. 2024; 15:1427443.

PMID: 39081326 PMC: 11286386. DOI: 10.3389/fimmu.2024.1427443.

Isolation, Culture, and Phenotypic Analysis of Murine Lung Organoids.

Evans K, Dabrowska C, Ng M, Brainson C, Lee J Methods Mol Biol. 2024; 2805:3-18.

PMID: 39008171 DOI: 10.1007/978-1-0716-3854-5_1.

References

Reynolds S, Hong K, Giangreco A, Mango G, Guron C, Morimoto Y . Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol. 2000; 278(6):L1256-63. DOI: 10.1152/ajplung.2000.278.6.L1256. View

Giangreco A, Reynolds S, Stripp B . Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol. 2002; 161(1):173-82. PMC: 1850682. DOI: 10.1016/S0002-9440(10)64169-7. View

Jones P, Simons B . Epidermal homeostasis: do committed progenitors work while stem cells sleep?. Nat Rev Mol Cell Biol. 2007; 9(1):82-8. DOI: 10.1038/nrm2292. View

Bender Kim C, Jackson E, Woolfenden A, Lawrence S, Babar I, Vogel S . Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005; 121(6):823-35. DOI: 10.1016/j.cell.2005.03.032. View

Warburton D, Wuenschell C, Anderson K . Commitment and differentiation of lung cell lineages. Biochem Cell Biol. 1999; 76(6):971-95. View

Gurtner G, Werner S, Barrandon Y, Longaker M . Wound repair and regeneration. Nature. 2008; 453(7193):314-21. DOI: 10.1038/nature07039. View

Rawlins E, Hogan B . Ciliated epithelial cell lifespan in the mouse trachea and lung. Am J Physiol Lung Cell Mol Physiol. 2008; 295(1):L231-4. PMC: 2494792. DOI: 10.1152/ajplung.90209.2008. View

Hong K, Reynolds S, Watkins S, Fuchs E, Stripp B . Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol. 2004; 164(2):577-88. PMC: 1602270. DOI: 10.1016/S0002-9440(10)63147-1. View

Rawlins E, Ostrowski L, Randell S, Hogan B . Lung development and repair: contribution of the ciliated lineage. Proc Natl Acad Sci U S A. 2006; 104(2):410-7. PMC: 1752191. DOI: 10.1073/pnas.0610770104. View

10.

Sangiorgi E, Capecchi M . Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008; 40(7):915-20. PMC: 2906135. DOI: 10.1038/ng.165. View

11.

Hong K, Reynolds S, Watkins S, Fuchs E, Stripp B . In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations. Am J Physiol Lung Cell Mol Physiol. 2003; 286(4):L643-9. DOI: 10.1152/ajplung.00155.2003. View

12.

Ventura J, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M . p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 2007; 39(6):750-8. DOI: 10.1038/ng2037. View

13.

Dor Y, Brown J, Martinez O, Melton D . Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 2004; 429(6987):41-6. DOI: 10.1038/nature02520. View

14.

Reynolds S, Giangreco A, Power J, Stripp B . Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol. 2000; 156(1):269-78. PMC: 1868636. DOI: 10.1016/S0002-9440(10)64727-X. View

15.

Hong K, Reynolds S, Giangreco A, Hurley C, Stripp B . 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. 2001; 24(6):671-81. DOI: 10.1165/ajrcmb.24.6.4498. View

16.

Schmidt G, Wilkinson M, Ponder B . Clonal analysis of chimaeric patterns in aortic endothelium. J Embryol Exp Morphol. 1986; 93:267-80. View

17.

Nolen-Walston R, Kim C, Mazan M, Ingenito E, Gruntman A, Tsai L . Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration. Am J Physiol Lung Cell Mol Physiol. 2008; 294(6):L1158-65. PMC: 2593913. DOI: 10.1152/ajplung.00298.2007. View

18.

Evans M, Freeman G . Role of the Clara cell in renewal of the bronchiolar epithelium. Lab Invest. 1978; 38(6):648-53. View

19.

Jones P, Simons B, Watt F . Sic transit gloria: farewell to the epidermal transit amplifying cell?. Cell Stem Cell. 2008; 1(4):371-81. DOI: 10.1016/j.stem.2007.09.014. View

20.

Clayton E, Doupe D, Klein A, Winton D, Simons B, Jones P . A single type of progenitor cell maintains normal epidermis. Nature. 2007; 446(7132):185-9. DOI: 10.1038/nature05574. View