西亚试剂：Haematopoietic stem cells depend on Gs-mediated signalling

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

Gregor B. Adams1,4,7, Ian R. Alley1, Ung-il Chung2,7, Karissa T. Chabner1, Nathaniel T. Jeanson1, Cristina Lo Celso1,4, Emily S. Marsters1, Min Chen6, Lee S. Weinstein6, Charles P. Lin3, Henry M. Kronenberg2 & David T. Scadden1,4,5

1 Center for Regenerative Medicine,
2 Endocrine Unit and,
3 Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
4 Harvard Stem Cell Institute,
5 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA
6 National Institute for Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA
7 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.).

Haematopoietic stem and progenitor cells (HSPCs) change location during development1 and circulate in mammals throughout life2, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention3, 4, 5. Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory  subunit (Gs). HSPCs from adult mice deficient in Gs (Gs -/-) 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, Gs deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of Gs affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. Gs governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically

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