Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow

Nature. 2009 May 7;459(7243):103-7. doi: 10.1038/nature07859. Epub 2009 Mar 25.


Haematopoietic stem and progenitor cells (HSPCs) change location during development and circulate in mammals throughout life, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention. Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory alpha subunit (Galpha(s)). HSPCs from adult mice deficient in Galpha(s) (Galpha(s)(-/-)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, Galpha(s) deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of Galpha(s) affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. Galpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / embryology
  • Bone Marrow / physiology*
  • Bone Marrow Transplantation / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cholera Toxin / pharmacology
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / physiology*


  • Adjuvants, Immunologic
  • Granulocyte Colony-Stimulating Factor
  • Cholera Toxin
  • GTP-Binding Protein alpha Subunits, Gs