Endogenous Fibroblastic Progenitor Cells in the Adult Mouse Lung Are Highly Enriched in the Sca-1 Positive Cell Fraction§

Authors

  • Jonathan L. McQualter,

    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
    2. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
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  • Nathalie Brouard,

    1. Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    2. Center for Stem Cell Research, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
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  • Brenda Williams,

    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
    2. Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
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  • Brandi N. Baird,

    1. Center for Stem Cell Research, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
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  • Sunder Sims-Lucas,

    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
    2. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
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  • Karen Yuen,

    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
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  • Susan K. Nilsson,

    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
    2. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
    3. Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    4. Pathology Department, University of Melbourne, Parkville, Victoria, Australia
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  • Paul J. Simmons,

    1. Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    2. Center for Stem Cell Research, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
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  • Ivan Bertoncello

    Corresponding author
    1. Australian Stem Cell Centre, Clayton, Victoria, Australia
    2. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
    3. Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    4. Pathology Department, University of Melbourne, Parkville, Victoria, Australia
    • Australian Stem Cell Centre, PO Box 8002, Monash University LPO, Victoria 3800, Australia
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    • Telephone: 61-3-9271-1174; Fax: 61-3-9271-1198


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

  • Author contributions: J.L.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; N.B.: conception and design, collection and/or assembly of data, data analysis and interpretation; B.W.: collection and/or assembly of data; B.N.B.: collection and/or assembly of data; S.S.-L.: collection and/or assembly of data; K.Y.: collection and/or assembly of data; S.K.N.: collection and/or assembly of data; P.J.S.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation; I.B.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • §

    First published online in STEM CELLSExpress December 11, 2008.

Abstract

Originally identified as a marker specifying murine hematopoietic stem cells, the Sca-1 antigen has since been shown to be differentially expressed by candidate stem cells in tissues including vascular endothelium, skeletal muscle, mammary gland, and prostate of adult mice. In the adult murine lung, Sca-1 has previously been identified as a selectable marker for the isolation of candidate nonhematopoietic (CD45), nonendothelial (CD31) bronchioalveolar stem cells (BASC) located at the bronchioalveolar duct junction that coexpress surfactant protein C and the Clara cell specific protein. Our systematic analysis of CD45CD31Sca-1+ cells in fetal, neonatal, and adult lung shows that very few of these cells are detectable prior to birth but expand exponentially postnatally coinciding with the transition from the saccular to the alveolar stage of lung development. Unlike candidate BASCs, the CD45CD31Sca-1+CD34+ cell fraction we describe coexpresses immunophenotypic markers (Thy-1 and platelet-derived growth factor receptor α) that define lung fibroblastic rather than epithelial cells. The mesenchymal “signature” of the CD45CD31Sca-1+CD34+ cell fraction is further confirmed by transcriptional profiling, by cell culture studies demonstrating enrichment for clonogenic lipofibroblastic and nonlipofibroblastic progenitors, and by immunohistochemical localization of Sca-1 in perivascular cells of the lung parenchyma. Although the CD45CD31Sca-1+CD34+ cell phenotype does define endogenous clonogenic progenitor cells in the adult murine lung, our data indicate that these progenitors are predominantly representative of mesenchymal cell lineages, and highlights the pressing need for the identification of alternative markers and robust functional assays for the identification and characterization of epithelial and fibroblastic stem and progenitor cell populations in the adult lung. STEM CELLS2009;27:623–633

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