Galphas信号通道是一个以前没有被发现在干细胞生物学中扮演一个角色的通道，现在它已被发现在发育中的胎儿和成年小鼠的造血作用中起关键作用。对发育中的胎儿，如果没有它，细胞就不会从胎儿肝脏过渡到骨髓中；对成年小鼠，如果没有它，细胞就不会嫁接到骨髓中。没有Galphas（全称：鸟嘌呤-核苷酸-结合蛋白刺激性alpha亚单元）的造血干细胞和祖细胞发生分化，并经历趋化作用，但不能寻址到它们通常的作用点上。
霍乱毒素（一种已知能够组成性地激活Galphas的化合物）在小鼠体内可增强干细胞的寻址和嫁接能力，说明类似的策略也有可能被用来提高移植器官中人的造血干细胞的效率。目前，临床器官移植中要使用数量巨大的造血干细胞，部分原因是寻址及嫁接效率低下。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 459, 103-107 (7 May 2009) | doi:10.1038/nature07859
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 targeted to improve transplantation efficiency.
