广州生物院阐明ANGPTL7促进造血干细胞扩增机理

　　

　1月30日，国际学术期刊Haematologica 在线发表了中国科学院广州生物医药与健康研究院李鹏研究组的最新研究成果ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells，该研究成果揭示了分泌蛋白ANGPLT7促进造血干细胞体外扩增和体内造血系统重建的机制。
　
　成功扩增造血干细胞可有效促进造血干细胞临床移植应用。一些类血管生成蛋白，如angiopoietin-like 7，可以提高造血干细胞增殖活性。然而，对ANGPTL7促进人体造血干细胞扩增作用及其激活的下游信号通路的了解却仍然不清晰。

    研究中，实验人员发现了一种可促进人造血干细胞和祖细胞扩增的鼠胚胎肝脏细胞系，该细胞特异性高表达Angptl7[l1] 蛋白。另外，研究还发现ANGPLT7蛋白可促进人体造血干细胞和祖细胞在异种移植宿主体内扩增和造血系统重建。RNA-Seq分析结果显示，ANGPTL7激活人体造血干细胞和组细胞中CXCR4、HOXB4和WNT下游靶点的表达。另外，通过化学调控WNT信号通路可以弱化ANGTPL7对人体造血干细胞和祖细胞的作用。

　　该研究发现了分泌生长因子ANGPTL7是人体造血干细胞和祖细胞扩增和造血重建的重要调节因子，对造血干细胞临床移植应用具有重要的指导意义。

 
 
ANGPTL7激活造血干细胞机制

原文摘要：

ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells

Successful expansion of hematopoietic stem cells would benefit the use of hematopoietic stem cell transplants in the clinic. Several angiopoietin-like proteins, including angiopoietin-like 7, can support the activity of hematopoietic stem cells. However, effects of ANGPTL7 on human hematopoietic stem cells and the downstream signaling cascade activated by ANGPTL7 are poorly understood. Here, we established a human hematopoietic stem and progenitor cell-supportive mouse fetal liver cell line that specifically expressed the Angptl7 protein. Furthermore, we found ANGPTL7 is capable of stimulating human hematopoietic stem and progenitor cell expansion and increasing the repopulation activities of human hematopoietic progenitors in xenografts. RNA-sequencing analysis showed that ANGPTL7 activated the expression of CXCR4, HOXB4 and Wnt downstream targets in human hematopoietic progenitors. In addition, chemical manipulation of Wnt signaling diminished the effects of ANGPTL7 on human hematopoietic stem and progenitor cells in culture. In summary, we identify the secreted growth factor ANGPTL7 as a regulator of both human hematopoietic stem and progenitor cells expansion and regeneration.