Karanu F N, Murdoch B, Miyabayashi T, Ohno M, Koremoto M, Gallacher L, Wu D, Itoh A, Sakano S, Bhatia M
Developmental Stem Cell Biology, The John P. Robarts Research Institute, London, ON, Canada.
Blood. 2001 Apr 1;97(7):1960-7. doi: 10.1182/blood.v97.7.1960.
Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (h Delta-1) and h Delta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that h Delta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human. (Blood. 2001;97:1960-1967)
Delta介导的Notch信号通路在无脊椎动物和小鼠发育过程中控制细胞命运的决定。然而，在人类中，Delta的功能作用尚未得到描述。本研究报告了人类Delta-1和Delta-4的特征。发现人类Delta-4在多种成人和胎儿组织中表达，包括造血部位。未成熟造血细胞亚群，以及支持造血的基质细胞和内皮细胞，均显示表达Notch以及Delta-1和Delta-4。人Delta-1（h Delta-1）和h Delta-4蛋白的可溶性形式能够在体外增强原始人类造血祖细胞的增殖。将处理后的培养物静脉内移植到免疫缺陷小鼠中发现，h Delta-1能够在体内扩增检测到的多能人类造血重建细胞。本研究首次提供了Delta配体作为人类原始造血细胞有丝分裂调节因子作用的证据。（《血液》。2001年；97:1960 - 1967）
