Very Small Embryonic-Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung

Authors

  • Susannah H. Kassmer,

    Corresponding author
    1. Department of Laboratory Medicine, and Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
    • Correspondence: Susannah H. Kassmer, Ph.D., Neuroscience Research Institute, University of California, Santa Barbara, California, USA. Telephone: 203-785-7089; e-mail: susannah.kassmer@lifesci.ucsb.edu

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  • Huiyan Jin,

    1. Department of Laboratory Medicine, and Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Ping-Xia Zhang,

    1. Department of Laboratory Medicine, and Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Emanuela M. Bruscia,

    1. Department of Pediatrics, and Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
    2. European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy
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  • Kartoosh Heydari,

    1. Department of Immunobiology, Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Joo-Hyeon Lee,

    1. Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
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  • Carla F. Kim,

    1. Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
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  • Diane S. Krause

    1. Department of Laboratory Medicine, and Yale Flow Cytometry Core Facility, Yale University School of Medicine, New Haven, Connecticut, USA
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  • This article was published online on 03 December 2013. Subsequently, it was determined that that the authorship was incomplete, and the correct authorship is shown above.

    Author contributions: S.K.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; H.J., P.-X.Z., K.H.: Collection and assembly of data; E.B.: data analysis and interpretation, and writing of manuscript; J.-H.L. and C.K.: provision of study material; D.K.: conception and design, data analysis and interpretation, and manuscript writing.

Abstract

The view that adult stem cells are lineage restricted has been challenged by numerous reports of bone marrow (BM)-derived cells giving rise to epithelial cells. Previously, we demonstrated that nonhematopoietic BM cells are the primary source of BM-derived lung epithelial cells. Here, we tested the hypothesis that very small embryonic like cells (VSELs) are responsible for this engraftment. We directly compared the level of BM-derived epithelial cells after transplantation of VSELs, hematopoietic stem/progenitor cells, or other nonhematopoietic cells. VSELs clearly had the highest rate of forming epithelial cells in the lung. By transplanting VSELs from donor mice expressing H2B-GFP under a type 2 pneumocyte-specific promoter, we demonstrate that this engraftment occurs by differentiation and not fusion. This is the first report of VSELs differentiating into an endodermal lineage in vivo, thereby potentially crossing germ layer lineages. Our data suggest that Oct4+ VSELs in the adult BM exhibit broad differentiation potential. STEM Cells 2013;31:2759–2766

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