Galphas信號(hào)通道是一個(gè)以前沒(méi)有被發(fā)現(xiàn)在干細(xì)胞生物學(xué)中扮演一個(gè)角色的通道,，現(xiàn)在它已被發(fā)現(xiàn)在發(fā)育中的胎兒和成年小鼠的造血作用中起關(guān)鍵作用,。對(duì)發(fā)育中的胎兒，如果沒(méi)有它,，細(xì)胞就不會(huì)從胎兒肝臟過(guò)渡到骨髓中,；對(duì)成年小鼠，如果沒(méi)有它,，細(xì)胞就不會(huì)嫁接到骨髓中,。沒(méi)有Galphas（全稱(chēng)：鳥(niǎo)嘌呤-核苷酸-結(jié)合蛋白刺激性alpha亞單元）的造血干細(xì)胞和祖細(xì)胞發(fā)生分化，并經(jīng)歷趨化作用,，但不能尋址到它們通常的作用點(diǎn)上,。
霍亂毒素（一種已知能夠組成性地激活Galphas的化合物）在小鼠體內(nèi)可增強(qiáng)干細(xì)胞的尋址和嫁接能力，說(shuō)明類(lèi)似的策略也有可能被用來(lái)提高移植器官中人的造血干細(xì)胞的效率,。目前,，臨床器官移植中要使用數(shù)量巨大的造血干細(xì)胞，部分原因是尋址及嫁接效率低下,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
