Robo4和Cxcr4协同作用于造血干细胞的niche定位

iseeyou1210

Title: Robo4和Cxcr4协同作用于造血干细胞的niche定位
6 b- `. ?  `& g  G. s5 `  T6 ~) gEnglish title:Robo4 Cooperates with Cxcr4 to Specify Hematopoietic Stem Cell Localization to Bone Marrow Niches! d( y; h/ Z- [7 W4 O
摘要：特定的骨髓微环境(niche)在维持造血干细胞的正常造血功能和干细胞移植治疗中起到重要的作用.在本研究中,作者指出定位分子ROBO4可以把造血干细胞引导到特定的微环境(niche)处.Robo4缺陷性的造血干细胞虽然保留了可以分化为多个谱系的造血细胞的能力,但是其造血干细胞在造血微环境的定位和长期造血系统重建的能力却减弱了.作者们还发现,在 Robo4−/−的造血干细胞中,为了补偿Robo4 gene 产物的缺失,Cxcr4这个调节干细胞定位的gene表达上调了.Robo4确实改变了干细胞的运动能力.他们的工作显示了Robo4和Cxcr4调节造血干细胞及其所处的微环境之间的相互作用在造血干细胞不的运动过程中起到重要功能.非常有趣的是,在正常的造血干细胞中,Cxcr4这个gene的表达却是很低的,而且Cxcr4看起来在其他的造血细胞(非干细胞)中的作用反而更为重要.根据这些实验,作者认为,Robo4和Cxcr4共同作用保持造血干细胞能结合到微环境中,作者提出可以在造血干细胞移植实验中,可以将Robo4作为一个治疗靶点。
7 p( B- ], s! E! m/ ?/ m英文摘要：Specific bone marrow (BM) niches are critical for hematopoietic stem cell (HSC) function during both normal hematopoiesis and in stem cell transplantation therapy. We demonstrate that the guidance molecule Robo4 functions to specifically anchor HSCs to BM niches. Robo4-deficient HSCs displayed poor localization to BM niches and drastically reduced long-term reconstitution capability while retaining multilineage potential. Cxcr4, a critical regulator of HSC location, is upregulated in Robo4−/− HSCs to compensate for Robo4 loss. Robo4 deletion led to altered HSC mobilization efficiency, revealing that inhibition of both Cxcr4- and Robo4-mediated niche interactions are necessary for efficient HSC mobilization. Surprisingly, we found that WT HSCs express very low levels of Cxcr4 and respond poorly to Cxcr4 manipulation relative to other hematopoietic cells. We conclude that Robo4 cooperates with Cxcr4 to endow HSCs with competitive access to limited stem cell niches, and we propose Robo4 as a therapeutic target in HSC transplantation therapy.) C" u% m& o- I$ o  @3 l
Note: 个人翻译，理解不准确的语句还望大家积极指出

nydfy

提供了不错的思路！

iseeyou1210

刚才有个大哥或者大姐,whatever了,给我指出了很多的问题的的帖子怎么不见了.