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Haematopoietic stem cells depend on Gαs-mediated signalling to engraft bone marrow

Author

Listed:
  • Gregor B. Adams

    (Center for Regenerative Medicine,
    Harvard Stem Cell Institute,
    Present addresses: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA (G.B.A.); Department of Bioengineering, Graduate Schools of Engineering and Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan (U.-i.C.).)

  • Ian R. Alley

    (Center for Regenerative Medicine,)

  • Ung-il Chung

    (Endocrine Unit and,
    Present addresses: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA (G.B.A.); Department of Bioengineering, Graduate Schools of Engineering and Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan (U.-i.C.).)

  • Karissa T. Chabner

    (Center for Regenerative Medicine,)

  • Nathaniel T. Jeanson

    (Center for Regenerative Medicine,)

  • Cristina Lo Celso

    (Center for Regenerative Medicine,
    Harvard Stem Cell Institute,)

  • Emily S. Marsters

    (Center for Regenerative Medicine,)

  • Min Chen

    (National Institute for Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA)

  • Lee S. Weinstein

    (National Institute for Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA)

  • Charles P. Lin

    (Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA)

  • Henry M. Kronenberg

    (Endocrine Unit and,)

  • David T. Scadden

    (Center for Regenerative Medicine,
    Harvard Stem Cell Institute,
    Harvard University, Cambridge, Massachusetts 02138, USA)

Abstract

Showing stem cells the way Gαs signalling, a pathway previously not recognized as having a role in stem-cell biology, has been found to be critical in haematopoiesis in the developing fetus (without it cells do not transition from the fetal liver to the bone marrow) and in adult mice (without it cells do not engraft the bone marrow). Haematopoietic stem and progenitor cells that lack Gαs (the guanine-nucleotide-binding protein stimulatory α subunit) differentiate and undergo chemotaxis, but are unable to home in on their usual sites of action. Cholera toxin, a compound known to constitutively activate Gαs, enhanced stem-cell homing and engraftment in mice, suggesting that similar strategies could be used to improve the efficiency in transplants of human blood-forming stem cells. Currently massive numbers of blood-forming stem cells are used in clinical transplantation, in part due to inefficient homing and engraftment.

Suggested Citation

  • Gregor B. Adams & Ian R. Alley & Ung-il Chung & Karissa T. Chabner & Nathaniel T. Jeanson & Cristina Lo Celso & Emily S. Marsters & Min Chen & Lee S. Weinstein & Charles P. Lin & Henry M. Kronenberg &, 2009. "Haematopoietic stem cells depend on Gαs-mediated signalling to engraft bone marrow," Nature, Nature, vol. 459(7243), pages 103-107, May.
    • Handle: RePEc:nat:nature:v:459:y:2009:i:7243:d:10.1038_nature07859
    DOI: 10.1038/nature07859
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