Airway Epithelial Progenitors Are Region Specific and Show Differential Responses to Bleomycin-Induced Lung Injury§

Authors

  • Huaiyong Chen,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Keitaro Matsumoto,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Brian L. Brockway,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Craig R. Rackley,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Jiurong Liang,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Joo-Hyeon Lee,

    1. Stem Cell Program, Children's Hospital Boston, Boston, Massachusetts, USA
    2. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
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  • Dianhua Jiang,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Paul W. Noble,

    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
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  • Scott H. Randell,

    1. Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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  • Carla F. Kim,

    1. Stem Cell Program, Children's Hospital Boston, Boston, Massachusetts, USA
    2. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
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  • Barry R. Stripp

    Corresponding author
    1. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Durham, North Carolina, USA
    2. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
    • 2075 MSRBII, 106 Research Drive, DUMC Box 103000, Durham, North Carolina 27710, USA. Telephone: 919-668-7762; Fax: 919-684-5266
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    • Fax: 919-684-5266


  • Author contributions: C.H., M.K., and S.B.R.: conception and design; S.B.R.: financial support; S.B.R.: provision of study material or patients; C.H., M.K., B.B.L., L.J., and S.B.R.: collection and/or assembly of data; C.H., M.K., R.C.R., B.B.L., K.C.F., L.J.H., and S.B.R.: data analysis and interpretation; C.H., M.K., R.C.R., J.D., N.P.W., R.S.H., K.C.F., and S.B.R.: manuscript writing; S.B.R.: final approval of manuscript. H.C. and K.M. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS June 13, 2012.

Abstract

Mechanisms that regulate regional epithelial cell diversity and pathologic remodeling in airways are poorly understood. We hypothesized that regional differences in cell composition and injury-related tissue remodeling result from the type and composition of local progenitors. We used surface markers and the spatial expression pattern of an SFTPC-GFP transgene to subset epithelial progenitors by airway region. Green fluorescent protein (GFP) expression ranged from undetectable to high in a proximal-to-distal gradient. GFPhi cells were subdivided by CD24 staining into alveolar (CD24neg) and conducting airway (CD24low) populations. This allowed for the segregation of three types of progenitors displaying distinct clonal behavior in vitro. GFPneg and GFPlow progenitors both yielded lumen containing colonies but displayed transcriptomes reflective of pseudostratified and distal conducting airways, respectively. CD24lowGFPhi progenitors were present in an overlapping distribution with GFPlow progenitors in distal airways, yet expressed lower levels of Sox2 and expanded in culture to yield undifferentiated self-renewing progeny. Colony-forming ability was reduced for each progenitor cell type after in vivo bleomycin exposure, but only CD24lowGFPhi progenitors showed robust expansion during tissue remodeling. These data reveal intrinsic differences in the properties of regional progenitors and suggest that their unique responses to tissue damage drive local tissue remodeling. Stem Cells2012;30:1948–1960

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