ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells
ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells
复制标题
ANGPTL7 调节人类造血干细胞和祖细胞的扩增和增殖
DOI：
10.3324/haematol.2014.118612
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发表时间：
2015-05-01
期刊：
影响因子：
10.1
通讯作者：
Li, Peng
中科院分区：
文献类型：
--
作者：
Xiao, Yiren;Jiang, Zhiwu;Li, Peng
造血干细胞的成功扩增将有利于造血干细胞移植在临床上的应用。几种血管生成素样蛋白，包括血管生成素样7，可以支持造血干细胞的活性。然而，ANGPTL7对人造血干细胞的作用和由ANGPTL7激活的下游信号级联反应知之甚少。在此，我们建立了特异性表达Angptl7蛋白的人造血干细胞和祖细胞支持的小鼠胎肝细胞系。此外，我们发现ANGPTL7能够刺激人造血干细胞和祖细胞扩增并增加异种移植物中人造血祖细胞的再增殖活性。RNA测序分析显示，ANGPTL7激活了人造血祖细胞中CXCR4、HOXB 4和Wnt下游靶标的表达。此外，Wnt信号传导的化学操作减弱了ANGPTL7对培养的人造血干细胞和祖细胞的影响。总之，我们鉴定了分泌的生长因子ANGPTL7作为人造血干细胞和祖细胞扩增和再生的调节因子。
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 cell expansion and regeneration.