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Fibronectin and VLA-4 in haematopoietic stem cell–microenvironment interactions

Naturevolume 352pages438441 (1991) | Download Citation

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Abstract

THE self-renewal and differentiation of haematopoietic stem cells occurs in vivo and in vitro in direct contact with cells making up the haematopoietic microenvironment1–4. In this study we used adhesive ligands and blocking antibodies to identify stromal cell-derived extracellular matrix proteins involved in promoting attachment of murine haematopoietic stem cells. Here we report that day-12 colony-forming-unit spleen (CFU-S12)5 cells and reconstituting haematopoietic stem cells attach to the C-terminal, heparin-binding fragment of fibronectin by recognizing the CS-1 peptide of the alternatively spliced non-type III connecting segment (IIICS) of human plasma fibronectin. Furthermore, CFU-S12 stem cells express the α4 subunit of the VLA-4 integrin receptor, which is known to be a receptor for the CS-1 sequence, and monoclonal antibodies against the integrin α4 subunit of VLA-4 block adhesion of CFU-S12 stem cells to plates coated with the C-terminal fibronectin fragment. Finally, polyclonal antibodies against the integrin β1 subunit of VLA-4 inhibit the formation of CFU-S12-derived spleen colonies and medullary haematopoiesis in vivo following intravenous infusion of antibody-treated bone marrow cells.

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Author notes

    • Carmella Stephens

    Present address: Memorial Sloan Kettering Institute, Rockefeller Institute, 67th Street, New York, New York, USA

    • David A. Williams

    Present address: Howard Hughes Medical Institute and Herman B Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, 46202-5225, USA

Affiliations

  1. Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA

    • David A. Williams
    • , Maribel Rios
    •  & Carmella Stephens
  2. Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA

    • David A. Williams
    • , Maribel Rios
    •  & Carmella Stephens
  3. Northwestern University, Evanston, Illinois, 60208, USA

    • Vikram P. Patel

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https://doi.org/10.1038/352438a0

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